Glutathione reductase deficiency in association with sickle cell and thalassaemia genes in Saudi populations

Glutathione reductase (GR) deficiency is reported to occur with a variable frequency in some populations of the world. In this study, the populations of two regions of Saudi Arabia which have a high frequency of sickle cell, thalassaemia and glucose-6-phosphate dehydrogenase (G-6-PD) deficiency, were screened for GR deficiency. Studies were also carried out to investigate the frequency of GR deficiency with other genetic blood disorders. The frequencies of complete GR deficiency were 0.0065 and 0.006, while those of partial deficiency were 0.146 and 0.074 in Al-Hafouf and Khaiber, respectively. GR deficiency was encountered in combination with the sickle gene, the G-6-PD deficiency gene and the thalassaemia gene in both regions. Individuals with GR deficiency showed slightly reduced haematological parameters. In thalassaemic/GR-deficient subjects, mean cell volume and mean cell haemoglobin were low, while in sickle cell anaemia patients with GR deficiency the haematological parameters were higher than in sickle cell anaemia patients without GR deficiency.     

Root exudation and Fe uptake and transport in wheat genotypes differing in tolerance to Zn deficiency

Tolerance to Zn deficiency in wheat germplasm may be inversely related to uptake and transport of Fe to shoots. The present study examined eight bread (Triticum aestivum) and two durum (T. turgidum L. conv. durum) wheat genotypes for their capacity to take up and transport Fe when grown under either Fe or Zn deficiency. Bread wheat genotypes Aroona, Excalibur and Stilleto showed tolerance to Zn and Fe deficiency, while durum wheat genotypes are clearly less tolerant to either deficiency. Roots of bread wheats tolerant to Zn deficiency exuded more phytosiderophores than sensitive bread and durum genotypes. Greater amounts of phytosideophores were exuded by roots grown under Fe than Zn deficiency. A relatively poor relationship existed between phytosiderophore exudation or the Fe uptake rate and relative shoot growth under Fe deficiency. At advanced stages of Zn deficiency, genotypes tolerant to Zn deficiency (Aroona and Stilleto) had a greater rate of Fe uptake than other genotypes. Zinc deficiency depressed the rate of Fe transport to shoots in all genotypes in early stages, while advanced Zn deficiency had the opposite effect. Compared with Zn-sufficient plants, 17-day-old Zn-deficient plants of genotypes tolerant to Zn deficiency had a lower rate of Fe transport to shoots, while genotypes sensitive to Zn deficiency (Durati, Yallaroi) had the Fe transport rate increased by Zn deficiency. A proportion of total amount of Fe taken up that was transported to shoots increased with duration of either Fe or Zn deficiency. It is concluded that greater tolerance to Zn deficiency among wheat genotypes is associated with the increased exudation of phytosiderophores, an increased Fe uptake rate and decreased transport of Fe to shoots. This revised version was published online in June 2006 with corrections to the Cover Date.     

Biochemical and clinical characteristics of creatine deficiency syndromes

Creatine deficiency syndromes are a newly described group of inborn errors of creatine synthesis (arginine:glycine amidinotransferase (AGAT) deficiency and guanidinoacetate methyltransferase (GAMT) deficiency) and of creatine transport (creatine transporter (CRTR) deficiency). The common clinical feature of creatine deficiency syndromes is mental retardation and epilepsy suggesting main involvement of cerebral gray matter. The typical biochemical abnormality of creatine deficiency syndromes is cerebral creatine deficiency, which is demonstrated by in vivo proton magnetic resonance spectroscopy. Measurement of guanidinoacetate in body fluids may discriminate between the GAMT (high concentration), AGAT (low concentration) and CRTR (normal concentration) deficiencies. Further biochemical characteristics include changes in creatine and creatinine concentrations in body fluids. GAMT and AGAT deficiency are treatable by oral creatine supplementation, while patients with CRTR deficiency do not respond to this type of treatment. The creatine deficiency syndromes are underdiagnosed, so their possibility should be considered in all children affected by unexplained mental retardation, seizures and speech delay.     

Estimation of the gene frequency of lactate dehydrogenase subunit deficiencies

To detect the frequency of lactate dehydrogenase (LDH) subunit deficiency, screening for LDH subunit deficiency was performed on 3,776 blood samples from healthy individuals in Shizuoka Prefecture by means of electrophoresis. The frequency of heterozygote with LDH-A subunit deficiency was found to be 0.185%, and with LDH-B subunit deficiency, 0.159%. The frequencies of both subunit deficiencies were not significantly different. Gene frequencies of LDH subunit deficiencies were calculated by the simple counting procedure, and the results are as follows: gene frequency of LDH-A subunit deficiency was 11.9 X 10(-4), and that of LDH-B subunit deficiency, 7.9 X 10(-4). In addition, the second case in the world of a homozygous individual with LDH-A subunit deficiency was detected by this screening. This case with regard to the characteristics of LDH-A subunit deficiency are summarized herein.     

Hyperammonemia related to carnitine metabolism with particular emphasis on ornithine transcarbamylase deficiency

Carnitine status was evaluated in 8 patients with partial ornithine transcarbamylase (OTC) deficiency and 19 patients with secondary carnitine deficiency, who were used as positive references. Laboratory findings indicated that all patients with OTC deficiency had secondary carnitine deficiency especially in hyperammonemic attack. After L-carnitine administration in 2 patients with OTC deficiency, the number of attacks was significantly reduced in both cases.     

Mechanisms associated with Fe‐deficiency tolerance and signaling in shoots of Pisum sativum

Mechanisms of Fe‐deficiency tolerance and signaling were investigated in shoots of Santi (deficiency tolerant) and Parafield (deficiency intolerant) pea genotypes using metabolomic and physiological approaches. From metabolomic studies, Fe deficiency induced significant increases in N‐, S‐ and tricarboxylic acid cycle metabolites in Santi but not in Parafield. Elevated N metabolites reflect an increase in N‐recycling processes. Increased glutathione and S‐metabolites suggest better protection of pea plants from Fe‐deficiency‐induced oxidative stress. Furthermore, Fe‐deficiency induced increases in citrate and malate in leaves of Santi suggests long‐distance transport of Fe is promoted by better xylem unloading. Supporting a role of citrate in the deficiency tolerance mechanism, physiological experiments showed higher Fe and citrate in the xylem of Santi. Reciprocal‐grafting experiments confirm that the Fe‐deficiency signal driving root Fe reductase and proton extrusion activity is generated in the shoot. Finally, our studies show that auxin can induce increased Fe‐reductase activity and proton extrusion in roots. This article identifies several mechanisms in shoots associated with the differential Fe‐deficiency tolerance of genotypes within a species, and provides essential background for future efforts to improve the Fe content and deficiency tolerance in peas.     

Indicators of erythrocyte formation and degradation in rats with either vitamin A or iron deficiency

Vitamin A deficiency produces anemia and altered iron status. In this study with rats we tested two hypotheses regarding vitamin A deficiency: (1) that it impairs erythropoiesis, leading to an increased red cell turnover, and (2) that it inhibits the glycosylation of transferrin. Erythropoietic activity was assessed indirectly by determining the myeloid:erythroid ratio in bone marrow smears, the number of erythroid colonies in the red pulp of spleen, the blood reticulocyte index, and zinc protoporphyrin and plasma transferrin receptor concentrations. Transferrin glycosylation was assessed by measuring the sialic acid content of transferrin. The effects of vitamin A deficiency were compared with those of iron deficiency. Iron deficiency produced anemia and low iron levels in organs. Vitamin A deficiency produced low levels of plasma and hepatic retinol, and it induced decreased plasma total iron-binding capacity and raised iron levels in tibia and spleen. Short- but not long-term iron deficiency reduced the number of erythroid colonies in spleen; vitamin A deficiency had no influence. Neither iron nor vitamin A deficiency influenced the myeloid:erythroid ratio in bone marrow smears and the blood reticulocyte production. Plasma transferrin receptor and erythrocyte zinc protoporphyrin concentrations were not affected by vitamin A deficiency but increased with iron deficiency. Vitamin A deficiency did not stimulate erythrocyte breakdown, as indicated by unaltered plasma lactate dehydrogenase activity and reduced plasma total bilirubin levels. Both vitamin A and iron deficiencies raised the proportion of multiple sialylated transferrins in plasma. Thus, we have not found evidence that vitamin A deficiency affects erythropoiesis and erythrocyte turnover. The iron accumulation in spleen and bone marrow may be related to reduced iron transport due to inhibition of transferrin synthesis rather than inhibition of transferrin sialylation.     

Vitamins and brain development.

Effects of deficiency of vitamins on early development of brain have been reviewed. Unusual developmental problems in neurogenesis specific for the brain and impairment of its functional capacities due to vitamin deficiency have been discussed. The species-specific "critical periods" in development of various systems have been mentioned. Indices such as reflex activity, locomotion, special senses, cognition and adaptive behavior were used for assessing brain maturation in experimental models and humans. Significant examples include brain anomalies in humans and other mammals caused by retinoid excess or deficit; increase in calbindin D28K, a vitamin D dependent calcium-binding protein during postnatal period in rat; hydrocephalus and exencephaly in prenatal rats and subarachnoidal or intracerebral hemorrhage in infants caused by vitamin E deficiency. Peripheral neuropathic lesions leading to infantile beriberi is caused by thiamine deficiency. Impaired growth in retinal layers leading to delay in maturation of electroretinogram and depth-perception in postnatal rats occur due to pyridoxine deficiency. Infants of severely vitamin B12 deficient mothers show abnormalities in behavior involving basal ganglia and pyramidal tract. Folic acid deficiency results in delayed maturation of the basic electroencepalographic patterns. In addition, vitamin-interactions leading to developmental errors have been pointed out. Vitamin B6 deficiency impairs vitamin B12 absorption and biotin deficiency may be aggravated by pantothenic acid deficiency. Vitamin C deficiency resulting in impaired metabolism may produce symptoms of deficiency of folic acid. Another characteristic examples is that iron absorption from dietary sources is dependent on ascorbic acid.     

The effect of nitrogen on plant water relations in tea (Camellia sinensis)

An experiment was carried out to study the effect of nitrogen deficiency on the water relations of tea (Camellia sinensis). The plants were grown in sand and nitrogen deficiency induced by witholding the supply of nitrogen. Nitrogen deficiency increased stomatal resistance and reduced transpiration. The capacity of the stomata to open fully in the morning was not impaired by nitrogen deficiency. Leaf water potential and probably root resistance were not affected by nitrogen deficiency. The sensitivity of transpiration and stomatal resistance to sand water stress was increased by nitrogen deficiency.     

Immunological characterization of a 36 kDa Fe deficiency specific peptide in barley roots

In a previous paper we reported that an acidic 36 kDa peptide is the most strongly induced peptide among several peptides induced by Fe deficiency in barley roots. In this paper, polyclonal antibodies were raised against the 36 kDa peptide. This peptide appeared in the roots of all the graminaceous species tested (barley, rye, wheat, oat, maize, sorghum and rice) in response to Fe deficiency. More of the peptide was found in the roots of graminaceous species which secrete higher amounts of mugineic acids (MAs) under Fe deficient nutrition status. Induction of the 36 kDa peptide was first observed on the third day of Fe deficiency, rising to a maximum value on the seventh day. The trend has a positive correlation with secretion of MAs during Fe deficiency. Further, resupply of Fe resulted in a decrease in peptide production on the second day, reaching a control level on the seventh day. The rate of decrease in peptide production was observed to be slower than that of MA secretion. Other nutrient stresses such as B excess, B deficiency, Cu excess, Cu deficiency, Mn excess, Mn deficiency, Zn excess and Zn deficiency induced far less of the peptide. The specific expression of the 36 kDa peptide in roots of graminaceous species under Fe deficiency suggested the positive association of the peptide with a specific Fe deficiency tolerance mechanism in graminaceous plants.     

The Influence of Magnesium Deficiency on the Growth of Chlorella

The growth of Chlorella in the magnesium deficient medium was postulated. It was found that magnesium deficiency has greater influence upon multiplication of cells than upon synthesis of cell materials. And the size of cells becomes larger in the magnesium deficient medium. Chlorophyll formation is completely suppressed by the deficiency. But it seems that growth is affected by magnesium deficiency itself rather than by chlorophyll deficiency caused by magnesium deficiency.     

A copper-deficiency-induced root reductase is different from the iron-deficiency-induced one in red clover (Trifolium pratense L.)

There is increasing evidence that Cu deficiency can induce root reductase activity, but the ecological and physiological significance of this is unknown. This study compared the characteristics of root reductase activity induced by Cu deficiency with those induced by Fe deficiency in red clover (Trifolium pratenseL. cv. Kenland), a Fe-efficient plant. Effects of other nutritional stresses were also investigated for comparison. Compared with the effect of Fe deficiency, Cu deficiency induced only a moderate level of root reductase activity, while other nutrient stresses had no effect, or even inhibited the root reductases activity, especially in the case of Zn deficiency. Compared with Fe deficiency-induced Fe(III)-chelate reductase, Cu deficiency-induced reductase displayed a different pattern of induction. The activity of the Cu deficiency-induced reductase in intact plants increased with time; in decapitated plants it showed a distinct peak at a later stage of the treatment. The Fe concentration in the roots was significantly increased under Cu deficiency. Furthermore, the reductase activity was presented in the entire root system, contrary to what was observed for the Fe-deficiency-induced reductase activity, which was confined to the root apex. Cu deficiency did not increase proton extrusion from the roots, even when growth was significantly affected. The present results suggest that in red clover Cu deficiency induces a root reductase that is different from the reductase induced by Fe deficiency.     

Decreased autophagy was implicated in the decreased apoptosis during decidualization in early pregnant mice

Folate deficiency is a major risk factor of birth defects. Mechanistic studies on folate deficiency resulting in birth defects have mainly focused on fetal development. There have been few studies on folate deficiency from the point of view of the mother’s uterus. In our previous study, we demonstrated that folate deficiency inhibits apoptosis of decidual cells, thereby restraining decidualization of the endometrium and impairing pregnancy. In this study, we further investigated the potential mechanism by which folate deficiency decreases endometrial apoptosis during decidualization. To investigate whether endometrium autophagy was inhibited under folate deficiency during decidualization, we performed real-time PCR for endometrial LC3 and P62 on day 6 (D6) to D8 of pregnancy in mice, and both were significantly changed compared to non-folate-deficient mice. Western blots showed that LC3-II and P62 were also changed in folate-deficient mice. Compared with control mice, a few punctuate LC3-II structures were detected in the folate deficiency group by immunofluorescence. Transmission electron micrographs of decidual cells on D8 showed that there were no evident autophagosomes in the folate deficiency group. In addition, apoptosis-related protein analysis by western blotting, TUNEL staining and flow cytometry showed that decreased endometrial apoptosis on D8 of pregnancy under folate deficiency was reversed after treatment with rapamycin, an autophagy inducer. ROS measurement showed that the endometrium ROS level was reduced by folate deficiency and that rapamycin reversed this effect on day 8 of pregnancy. All the results suggest that inhibiting endometrial autophagy may be implicated in the decreased endometrial apoptosis under folate deficiency during decidualization.     

Effect of riboflavin or pyridoxine deficiency on inflammatory response.

Inflammatory response has been assessed in riboflavin or pyridoxine deficient rats. Edema was increased by 54% in pyridoxine deficiency as compared to weight-matched control rats. Food restriction per se reduced the volume of edema by 63%. In pyridoxine deficiency, concentrations of thiobarbituric acid reactive substances (which indicate the extent of lipid peroxidation) increase by 30 and 43% respectively in the edematous tissues of the paw as well as in the wounded skin. Both these parameters were not affected by riboflavin deficiency. Activities of NADPH oxidase and superoxide dismutase in elicited leukocytes from peritoneal cavity were reduced by 54 and 52%, respectively, in riboflavin deficiency but were unaltered in pyridoxine deficiency. Superoxide level and acid phosphatase activity were not influenced by either of the deficiencies, whereas hydrogen peroxide level was increased by 48% in riboflavin deficiency. Food restriction did not affect leukocyte enzymes or the levels of reduced oxygen species. The data suggest that inflammation is enhanced in pyridoxine deficiency but not in riboflavin deficiency.     

Rare deficiency types of alpha 1-antitrypsin: electrophoretic variation and DNA haplotypes.

A deficiency of the plasma protease inhibitor alpha 1-antitrypsin (alpha 1AT), is usually associated with the deficiency allele PI*Z. However, other alleles can also produce a deficiency. Some of these rare deficiency alleles produce a low concentration (3%-15% of normal) of alpha 1AT and include Mmalton, Mduarte, Mheerlen, and Mprocida. Null, or nonproducing, alleles are associated with trace amounts (less than 1%) of plasma alpha 1AT. We have identified, using isoelectric focusing, the deficiency alleles in 222 patients (68 children and 154 adults) with alpha 1AT deficiency. In addition to PI*Z, we found low-producing alleles PI*Mmalton and PI*Mcobalt and four null (PI*QO) alleles. On the basis of a population frequency of .0122 for PI*Z, frequencies for other deficiency alleles are 1.1 x 10(-4) for PI*Mmalton, 2.5 x 10(-5) for PI*Mcobalt (which may be the same as that for PI*Mduarte, and 1.4 x 10(-4) for all null alleles combined. Using 12 polymorphic restriction sites with seven different restriction enzymes, we have obtained DNA haplotypes for each of the rare deficiency types. All of the rare deficiency alleles can be distinguished from PI*Z by their DNA haplotype, and most can be distinguished from each other. DNA haplotypes are useful to indicate the presence of new types of null alleles, to identify genetic compounds for rare deficiency alleles, and to identify the original normal allele from which each deficiency allele is derived.     

Effect of nitrogen deficiency on antioxidant status and Cd toxicity in rice seedlings

Effect of nitrogen (N) deficiency on antioxidant status and Cd toxicity in rice seedlings was investigated. N deficiency resulted in a reduction of shoot growth but not root growth. The contents of N-containing compounds such as nitrate, chlorophyll, and protein decreased in leaves of rice seedlings grown under N deficiency. Accumulation of abscisic acid and H₂O₂ in leaves was induced by N deficiency. The content of ascorbate and the activities of ascorbate peroxidase, glutathione reductase, and catalase in N-deficient leaves were lower than their respective control leaves. However, glutathione content was not affected and superoxide dismutase activity was increased by N deficiency. Cd toxicity in N-deficient seedlings was more pronounced than that in N-sufficient ones. Pretreatment with ascorbate or L-galactono-1,4-lactone, a biosynthetic precursor of ascorbate resulted in a reduction of Cd toxicity enhanced by N deficiency. N deficiency also resulted in an enhancement of Cd uptake in rice seedlings. The possible mechanism of Cd toxicity enhanced by N deficiency is discussed.     

2型糖尿病患者中医证型与糖脂代谢和甲状腺功能的关系

目的:探讨2型糖尿病患者中医证型与糖脂代谢和甲状腺功能的关系。方法:选择2016年1月-2017年12月期间武警宁夏总队医院收治的2型糖尿病患者104例,根据中医证型将其分为湿热困脾组23例、阴虚热盛组21例、气阴两虚组20例、阴阳两虚组22例与血瘀脉络组18例。检测并对比不同中医证型2型糖尿病患者糖脂代谢与甲状腺功能指标水平。结果:阴虚热盛组、气阴两虚组、阴阳两虚组与血瘀脉络组甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)水平低于湿热困脾组,高密度脂蛋白胆固醇(HDL-C)水平高于湿热困脾组(P0.05);阴阳两虚组TG、TC、LDL-C水平低于阴虚热盛组、气阴两虚组、血瘀脉络组(P0.05)。湿热困脾组、气阴两虚组、阴阳两虚组与血瘀脉络组空腹血糖(FPG)、餐后2h血糖(2hPPG)、糖化血红蛋白(GHb)水平低于阴虚热盛组(P0.05)。湿热困脾组、阴虚热盛组、气阴两虚组、血瘀脉络组游离甲状腺素(FT4)、游离三碘甲状腺原氨酸(FT3)水平高于阴阳两虚组,促甲状腺激素(TSH)水平低于阴阳两虚组(P0.05),各组总甲状腺素(TT4)、总三碘甲状腺原氨酸(TT3)水平总体比较差异无统计学意义(P0.05)。结论:糖脂代谢和甲状腺功能能够在一定程度上反映出2型糖尿病患者的中医证型变化,可作为2型糖尿病患者中医证型与病情变化的有效参考指标。     

Thirteen Years Experience with Selective Screening for Disorders in Purine and Pyrimidine Metabolism

Purine and pyrimidine disorders represent a heterogeneous group with variable clinical symptoms and low prevalence rate. In the last thirteen years, we have studied urine/plasma specimens from about 1600 patients and we have identified 35 patients: eight patients with adenylosuccinate lyase deficiency, eight patients with hypoxanthine-guanine phosphoribosyltransferase deficiency, one patient with purine nucleoside phosphorylase deficiency, ten patients with xanthine dehydrogenase deficiency, six patients with molybdenum cofactor deficiency and two patients with dihydropyrimidine dehydrogenase deficiency.

Despite low incidence of these diseases, our findings highlight the importance of including the purine and pyrimidine analysis in the selective screening for inborn errors of metabolism in specialized laboratories, where amino acid and organic acid disorders are simultaneously investigated.     

Changes in the anatomical structure of the first two leaves of barley caused by the absence of nitrogen or phosphorus in the nutrient medium

The absence of nitrogen or phosphorus in the nutrient medium affected quantitative anatomical characteristics of the first two leaves of spring barley: nitrogen deficiency brought about changes in both the leaf size and characteristics of stomata, whereas the effect of phosphorus absence was insignificant. N deficiency had an opposite effect on certain characteristics connected with volume ratios of tissues than that of P. The most marked finding is the decrease in the leaf volume and specific volume, and in specific volumes of most tissues at N deficiency and their increase at P deficiency. On the other hand, the number of stomata per unit leaf or photosynthetic tissue volume increased as the result of N deficiency and decreased at P deficiency.