The crystal and molecular structure of thiamine hydroiodide /|nWilliam Edward Lee. -- 260 St. Catharines [Ont.] : Dept. of Chemistry, Brock University,

The x-ray crystal structure of thiamine hydroiodide,C1ZH18N40S12' has been determined. The unit cell parameters are a = 13.84 ± 0.03, o b = 7.44 ± 0.01, c = 20.24 ± 0.02 A, 8 = 120.52 ± 0.07°, space group P2/c, z = 4. A total of 1445 reflections having ,2 > 2o(F2), 26 < 40° were collected on a Picker four-circle diffractometer with MoKa radiation by the 26 scan technique. The structure was solved by the heavy atom method. The iodine and sulphur atoms were refined anisotropically; only the positional parameters were refined for the hydrogen atoms. Successive least squares cycles yielded an unweighted R factor of 0.054. The site of protonation of the pyrimidine ring is the nitrogen opposite the amino group. The overall structure conforms very closely to the structures of other related thiamine compounds. The bonding surrounding the iodine atoms is distorted tetrahedral. The iodine atoms make several contacts with surrounding atoms most of them at or near the van der Waal's distances A thiaminium tetrachlorocobaltate salt was produced whose molecular and crystal structure was j~dged to be isomorphous to thiaminium tetrachlorocadmate.

Mechanisms of lipid malabsorption in Cystic Fibrosis: the impact of essential fatty acids deficiency

Affiliation: CHU-Sainte-Justine, Université de Montréal

Impact of (pro)renin receptor deficiency in adipose tissue using a genetically engineered mouse model

La stimulation du récepteur de la rénine/prorénine [(P) RR], un membre récemment découvert du système rénine-angiotensine (SRA), augmente l'activité du SRA et des voies de signalisation angiotensine II-indépendante. Pour étudier l'impact potentiel du (P)RR dans le développement de l`obésité, nous avons émis l'hypothèse que les souris déficientes en (P)RR uniquement dans le tissus adipeux (KO) auront une diminution du poids corporel en ciblant le métabolisme du tissu adipeux, l'activité locomoteur et/ou la prise alimentaire. Ainsi, des souris KO ont été générées en utilisant la technologie Cre/Lox. Le gain de poids et la prise alimentaire ont été évalués hebdomadairement dans les mâles et femelles KO et de type sauvage (WT) pendant 4 semaines alors qu’ils étaient maintenu sur une diète normal. De plus, un groupe de femelles a été placé pour 6 semaines sur une diète riche en gras et en glucides (HF/HC). La composition corporelle et l'activité ambulatoire ont été évaluées par l’EchoMRI et à l’aide de cages Physioscan, respectivement. Les tissus adipeux ont été prélevés et pesés. De plus, les gras péri-gonadaux ont été utilisés pour le microarray. Finalement, le niveaux d'expression d'ARNm du (P)RR ont été évalués. Comme le gène du (P)RR est situé sur le chromosome X, les mâles étaient des KOs complets et les femelles étaient des KOs partielles. Les souris KO avaient un poids corporel significativement plus petit par rapport à WT, les différences étant plus prononcées chez les mâles. De plus, les femelles KOs étaient résistantes à l'obésité lorsqu'elles ont été placées sur la diète HF/HC et donc elles avaient significativement moins de masse grasse par rapport aux WTs. L’analyse histologique des gras péri-gonadaux des KOs nous ont dévoilés qu’il avait une réduction du nombre d'adipocytes mais de plus grande taille. Bien qu'il n'y ait eu aucun changement dans la consommation alimentaire, une augmentation de près de 3 fois de l'activité ambulatoire a été détectée chez les mâles. De plus, nous avons observé que leurs tibias étaient de longueur réduite ce qui suggère fortement l'affection de leur développement. Les gras péri-gonadaux des souris KO avaient une expression réduite de l`ABLIM2 (Actin binding LIM protein family, member 2) qui est associé avec le diabète de type II chez l'humain. Ainsi, les données recueillies suggèrent fortement que le (P)RR est impliquée dans la régulation du poids corporelle.

Warfarin-induced vitamin K deficiency is associated with cognitive and behavioral perturbations, and alterations in brain sphingolipids in rats

La Vitamine K (VK) est largement reconnue pour son rôle dans la coagulation sanguine toutefois, de plus en plus de travaux indiquent son implication dans la fonction cérébrale. La VK est requise pour l'activation de différentes protéines, par exemple la protéine Gas6, et la ménaquinone-4 (MK-4), le principal vitamère K dans le cerveau, est impliquée dans le métabolisme des sphingolipides. Dans un rapport précédent, nous avons montré qu'un régime alimentaire faible en VK tout au long de la vie était associé à des déficits cognitifs chez des rats âgés. La warfarine sodique est un puissant antagoniste de la VK qui agit en bloquant le cycle de la VK, provoquant un «déficit relatif de VK » au niveau cellulaire. À la lumière du rôle émergent de la VK dans le cerveau, la warfarine pourrait représenter un facteur de risque pour la fonction cérébrale. Ce travail est donc pertinente en raison de la forte proportion d'adultes traîtés à la warfarine sodique. Dans la présente étude, 14 rats mâles Wistar ont été traités avec 14 mg de warfarine/kg /jour (dans l'eau potable) et des injections sous-cutanées de VK (85 mg/kg), 3x/sem, pendant 10 semaines. Quatorze rats témoins ont été traités avec de l'eau normale et injectés avec une solution saline. Les rats ont été soumis à différents tests comportementaux après quoi les niveaux de phylloquinone, MK-4, sphingolipides (cérébroside, sulfatide, sphingomyéline, céramide et gangliosides), et les sous-types de gangliosides (GT1b, GD1a, GM1, GD1b), ont été évalués dans différentes régions du cerveau. Comparativement aux rats du groupe contrôle, les rats traités à la warfarine présentaient des latences plus longues au test de la piscine de Morris (p <0,05) ainsi qu'une hypoactivité et un comportement exploratoire plus faible au test de « l’open field » (p <0,05). Le traitement par warfarine a également entraîné une diminution spectaculaire du niveau de MK-4 dans toutes les régions du cerveau (p <0,001), une altération des concentrations de sphingolipidiques, en particulier dans le cortex frontal et le mésencéphale (p <0,05), et une perte de différences régionales sphingolipidiques, notamment pour les gangliosides. Le traitement par warfarine a été associé à un niveau inférieur de GD1a dans l'hippocampe et un niveau supérieur de GT1b dans le cortex préfrontal et le striatum. En conclusion, la déficience en VK induite par warfarine altère les niveaux de VK et sphingolipides dans le cerveau, avec de potentiels effets néfastes sur les fonctions cérébrales.

Neuroendocrinology of Pyridoxine Deficiency

Veuruenducrim lri v j p .rim, deficienc:v. NEUROSCI BIOBEHAV REV 12(3/4) 189-193. 1988.- Dihydroxyphenylalanine decarboxvlase and 5-hydroxytryptophan decarboxvlase respectively have high and low affinities for pyridoxal phosphate. In the pyridoxinedeficient animal. hypothalamic serotonin content is significantly reduced without any change in catecholamine levels. Hypothalamic neurotransmitters affect the hvpothalamo-pituitary-end organ axes. Specifically, the decrease in hypothalamic serotonin in the pyridoxine-deficient rat results in tertiary hypothyroidism. In addition. pineal function is affected in deficient animals due to decreased synthesis of melatonin.

Hypertension in Pyridoxine Deficiency

Pyridoxal phosphate (PLP) is the coenzyme of various decarboxylases involved in the formation of monoamine urotransmitters such as y-aminobulyric acid (GAE3A), serotonin (5-HT) and dopamine. 1-lowever; in the pyridoxine-deficient rats GABA and 5-HT are decreased in various brain areas including the hypothalamus, with no change in the catecholamine levels. Serotonin and GABA are known to be involved in blood pressure control mechanisms. In this study adult Sprague-Dawley rats placed on a pyridoxine-deficient diet for 8 weeks showed significant hypertension compared with pyridoxine-supplemented controls. This was associated with a general sympathetic stimulation. Treatment of deficient rats with a single dose of pyridoxine (10 mg/kg body weight) reversed the blood pressure to normal levels within 24 h, with concomitant restoration of hypothalamic 5-HT and GABA, as well as the return of plasma norepinephrine to nornr;l levels. The results indicate that there is a cause-and-effect relationship between pyridoxine deficiency and hypertension.

Effect of Pyridoxine Deficiency in Young-Rats on High-Affinity Serotonin and Dopamine Receptors

The high-affinity bindings of [3H]-5-hydroxytryptamine to serotonin S-1 receptors, [3H]-ketanserin to serotonin S-2 receptors in the cerebral cortex, [3H]- fluphenazine to dopamine D-1 receptors, and [3H]-spiroperidol to dopamine D-2 receptors in the corpus striatum were studied in pyridoxine-deficient rats and compared to pyridoxine-supplemented controls. There was a significant increase in the maximal binding (Bmax) of serotonin S-1 and S-2 receptors with a significant decrease in their binding affinities (Kd). However, there were no significant changes either in the maximal binding or binding affinity of striatal dopamine D- 1 and D-2 receptors. Receptor sensitivity seems to correlate negatively with the corresponding neurotransmitter concentrations in the pyridoxine-deficient rats.

Professional Services: Civil Liability for Deficiency

This study deals the professional Services civil Liability for deficiency with special reference to medical professionals.the study deals with the characteristics of profession,basis of liability , historical evolution of legal controls on professional services, liability of doctors for negligence under tort law. Expectations to liability for medical negligence are critically evaluated. consent of medical treatment etc are studied

Soil factors associated with zinc deficiency in crops and humans

Zinc deficiency is the most ubiquitous micronutrient deficiency problem in world crops. Zinc is essential for both plants and animals because it is a structural constituent and regulatory co-factor in enzymes and proteins involved in many biochemical pathways. Millions of hectares of cropland are affected by Zn deficiency and approximately one-third of the human population suffers from an inadequate intake of Zn. The main soil factors affecting the availability of Zn to plants are low total Zn contents, high pH, high calcite and organic matter contents and high concentrations of Na, Ca, Mg, bicarbonate and phosphate in the soil solution or in labile forms. Maize is the most susceptible cereal crop, but wheat grown on calcareous soils and lowland rice on flooded soils are also highly prone to Zn deficiency. Zinc fertilizers are used in the prevention of Zn deficiency and in the biofortification of cereal grains.

Zinc deficiency in selected cultivars of wheat and barley as tested in solution culture

The relative zinc (Zn) efficiencies of 33 wheat and 3 barley cultivars were determined by growing them in chelate-buffered culture solutions. Zn efficiency, determined by growth in a Zn-deficient solution relative to that in a medium containing an adequate concentration of Zn, was found to vary between 10% and 63% among the cultivars tested. Out of the 36 cultivars tested, 12 proved to be Zn efficient, 10 were Zn inefficient, and the remaining 14 varieties were classed as intermediate. The most Zn-efficient cultivars included Bakhtawar, Gatcher S61, Wilgoyne, and Madrigal, and the most Zn inefficient included Durati, Songlen, Excalibur, and Chakwal-86. Zn-efficient cultivars accumulated greater amounts of Zn in their shoots than inefficient cultivars, but the correlation between shoot Zn and shoot dry matter production was poor. All the cultivars accumulated higher concentrations of iron (Fe), copper (Cu), manganese (Mn), and phosphorus (P) at deficient levels of Zn, compared with adequate Zn concentrations. The Zn-inefficient cultivars accumulated higher concentrations of these other elements compared to efficient cultivars.

The illusion of environmental iodine deficiency

The distribution of endemic goitre in England and Wales was compared with the distribution of environmental iodine (atmospheric deposition, soil, surface water). Despite a very clear goitre belt through the west of England and Wales there was no patterning in the environmental iodine distribution. A clear seasonal variation in depositional iodine exists, with an unusually high concentration of iodine in March 1997. The temporal variation in iodine concentration is determined at the monthly and not the annual level. The presence of endemic goitre is no indicator of how iodine is distributed in the environment or vice versa!

Will rising household incomes solve China's micronutrient deficiency problems?

Rapid economic growth in China has resulted in substantially improved household incomes. Diets have also changed, with a movement away from traditional foods and towards animal products and processed foods. Yet micronutrient deficiencies, particularly for calcium and vitamin A, are still widespread in China. In this research we model the determinants of the intakes of these micronutrients using household panel data, asking particularly whether continuing income increases are likely to cause the deficiencies to be overcome. Nonparametric kernel regressions and random effects panel regression models are employed. The results show a statistically significant but relatively small positive income effect on both nutrient intakes. The local availability of milk is seen to have a strong positive effect on intakes of both micronutrients. Thus, rather than relying on increasing incomes to overcome deficiencies, supplementary government policies, such as school milk programmes, may be warranted.

Thiamine is synthesized by a salvage pathway in Rhizobium leguminosarum bv. viciae strain 3841

In the absence of added thiamine, Rhizobium leguminosarum bv. viciae strain 3841 does not grow in liquid medium and forms only "pin" colonies on agar plates, which contrasts with the good growth of Sinorhizobium meliloti 1021, Mesorhizobium loti 303099, and Rhizobium etli CFN42. These last three organisms have thiCOGE genes, which are essential for de novo thiamine synthesis. While R. leguminosarum bv. viciae 3841 lacks thiCOGE, it does have thiMED. Mutation of thiM prevented formation of pin colonies on agar plates lacking added thiamine, suggesting thiamine intermediates are normally present. The putative functions of ThiM, ThiE, and ThiD are 4-methyl-5-(beta-hydroxyethyl) thiazole (THZ) kinase, thiamine phosphate pyrophosphorylase, and 4-amino-5-hydroxymethyl-2-methyl pyrimidine (HMP) kinase, respectively. This suggests that a salvage pathway operates in R. leguminosarum, and addition of HMP and THZ enabled growth at the same rate as that enabled by thiamine in strain 3841 but elicited no growth in the thiM mutant (RU2459). There is a putative thi box sequence immediately upstream of the thiM, and a gfp-mut3.1 fusion to it revealed the presence of a promoter that is strongly repressed by thiamine. Using fluorescent microscopy and quantitative reverse transcription-PCR, it was shown that thiM is expressed in the rhizosphere of vetch and pea plants, indicating limitation for thiamine. Pea plants infected by RU2459 were not impaired in nodulation or nitrogen fixation. However, colonization of the pea rhizosphere by the thiM mutant was impaired relative to that of the wild type. Overall, the results show that a thiamine salvage pathway operates to enable growth of Rhizobium leguminosarum in the rhizosphere, allowing its survival when thiamine is limiting.