Alginate Inhibits Iron Absorption from Ferrous Gluconate in a Randomized Controlled Trial and Reduces Iron Uptake into Caco-2 Cells

Previous in vitro results indicated that alginate beads might be a useful vehicle for food iron fortification. A human study was undertaken to test the hypothesis that alginate enhances iron absorption. A randomised, single blinded, cross-over trial was carried out in which iron absorption was measured from serum iron appearance after a test meal. Overnight-fasted volunteers (n = 15) were given a test meal of 200 g cola-flavoured jelly plus 21 mg iron as ferrous gluconate, either in alginate beads mixed into the jelly or in a capsule. Iron absorption was lower from the alginate beads than from ferrous gluconate (8.5% and 12.6% respectively, p = 0.003). Sub-group B (n = 9) consumed the test meals together with 600 mg calcium to determine whether alginate modified the inhibitory effect of calcium. Calcium reduced iron absorption from ferrous gluconate by 51%, from 11.5% to 5.6% (p = 0.014), and from alginate beads by 37%, from 8.3% to 5.2% (p = 0.009). In vitro studies using Caco-2 cells were designed to explore the reasons for the difference between the previous in vitro findings and the human study; confirmed the inhibitory effect of alginate. Beads similar to those used in the human study were subjected to simulated gastrointestinal digestion, with and without cola jelly, and the digestate applied to Caco-2 cells. Both alginate and cola jelly significantly reduced iron uptake into the cells, by 34% (p = 0.009) and 35% (p = 0.003) respectively. The combination of cola jelly and calcium produced a very low ferritin response, 16.5% (p<0.001) of that observed with ferrous gluconate alone. The results of these studies demonstrate that alginate beads are not a useful delivery system for soluble salts of iron for the purpose of food fortification.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01528644","term_id":"NCT01528644"}}NCT01528644     

Nicotianamine,a Novel Enhancer of Rice Iron Bioavailability to Humans

Background

Polished rice is a staple food for over 50% of the world''s population, but contains little bioavailable iron (Fe) to meet human needs. Thus, biofortifying the rice grain with novel promoters or enhancers of Fe utilization would be one of the most effective strategies to prevent the high prevalence of Fe deficiency and iron deficiency anemia in the developing world.

Methodology/Principal Findings

We transformed an elite rice line cultivated in Southern China with the rice nicotianamine synthase gene (OsNAS1) fused to a rice glutelin promoter. Endosperm overexpression of OsNAS1 resulted in a significant increase in nicotianamine (NA) concentrations in both unpolished and polished grain. Bioavailability of Fe from the high NA grain, as measured by ferritin synthesis in an in vitro Caco-2 cell model that simulates the human digestive system, was twice as much as that of the control line. When added at 1∶1 molar ratio to ferrous Fe in the cell system, NA was twice as effective when compared to ascorbic acid (one of the most potent known enhancers of Fe bioavailability) in promoting more ferritin synthesis.

Conclusions

Our data demonstrated that NA is a novel and effective promoter of iron utilization. Biofortifying polished rice with this compound has great potential in combating global human iron deficiency in people dependent on rice for their sustenance.     

A Self-microemulsifying Drug Delivery System (SMEDDS) for a Novel Medicative Compound Against Depression: a Preparation and Bioavailability Study in Rats

AJS is the code name of an untitled novel medicative compound synthesized by the Tasly Holding Group Company (Tianjin, China) based on the structure of cinnamamide, which is one of the Biopharmaceutics Classification System (BCS) class II drugs. The drug has better antidepressant effect, achieved by acting on the 5-hydroxytryptamine receptor. However, the therapeutic effects of the drug are compromised due to its poor water solubility and lower bioavailability. Herein, a self-microemulsifying drug delivery system (SMEDDS) was developed to improve its solubility and oral bioavailability. AJS-SMEDDS formulation was optimized in terms of drug solubility in the excipients, droplet size, stability, and drug precipitation using a pseudo-ternary diagram. The pharmacokinetic study was performed in rats, and the drug concentration in plasma samples was assayed using the high-performance liquid chromatography-electrospray tandem mass spectrometry (HPLC-MS/MS) method. The optimized formulation for SMEDDS has a composition of castor oil 24.5%, Labrasol 28.6%, Cremphor EL 40.8%, and Transcutol HP 2.7% (co-surfactant). No drug precipitation or phase separation was observed from the optimized formulation after 3 months of storing at 25°C. The droplet size of microemulsion formed by the optimized formulation was 26.08 ± 1.68 nm, and the zeta potential was −2.76 mV. The oral bioavailability of AJS-SMEDDS was increased by 3.4- and 35.9-fold, respectively, compared with the solid dispersion and cyclodextrin inclusion; meanwhile, the C_max of AJS-SMEDDS was about 2- and 40-fold as great as the two controls, respectively. In summary, the present SMEDDS enhanced oral bioavailability of AJS and was a promising strategy to orally deliver the drug.KEY WORDS: bioavailability, HPLC-MS/MS, self-microemulsifying drug delivery system, solubilization, stability     

Characterization of a Novel Anti-Cancer Compound for Astrocytomas

The standard chemotherapy for brain tumors is temozolomide (TMZ), however, as many as 50% of brain tumors are reportedly TMZ resistant leaving patients without a chemotherapeutic option. We performed serial screening of TMZ resistant astrocytoma cell lines, and identified compounds that are cytotoxic to these cells. The most cytotoxic compound was an analog of thiobarbituric acid that we refer to as CC-I. There is a dose-dependent cytotoxic effect of CC-I in TMZ resistant astrocytoma cells. Cell death appears to occur via apoptosis. Following CC-I exposure, there was an increase in astrocytoma cells in the S and G2/M phases. In in vivo athymic (nu/nu) nude mice subcutaneous and intracranial tumor models, CC-I completely inhibited tumor growth without liver or kidney toxicity. Molecular modeling and enzyme activity assays indicate that CC-I selectively inhibits topoisomerase IIα similar to other drugs in its class, but its cytotoxic effects on astrocytoma cells are stronger than these compounds. The cytotoxic effect of CC-I is stronger in cells expressing unmethylated O⁶-methylguanine methyltransferase (MGMT) but is still toxic to cells with methylated MGMT. CC-I can also enhance the toxic effect of TMZ on astrocytoma when the two compounds are combined. In conclusion, we have identified a compound that is effective against astrocytomas including TMZ resistant astrocytomas in both cell culture and in vivo brain tumor models. The enhanced cytotoxicity of CC-I and the safety profile of this family of drugs could provide an interesting tool for broader evaluation against brain tumors.     

Design and Evaluation of a Novel Evodiamine-Phospholipid Complex for Improved Oral Bioavailability

A novel evodiamine (EVO)-phospholipid complex (EPLC) was designed to improve the bioavailability of EVO. A central composite design approach was employed for process optimization. EPLC were characterized by differential scanning calorimetry, ultraviolet spectroscopy, Fourier transformed infrared spectroscopy, ¹H-NMR spectroscopy, matrix-assisted laser desorption/ionization time-of-flight spectroscopy, apparent solubility, and dissolution rate. After oral administration of EPLC, the concentrations of EVO at different time points were determined by high-performance liquid chromatography. The optimal formulation for EPLC was obtained where the values of X₁, X₂, and X₃ were 2, 0.5, and 2.5 mg/mL, respectively. The average particle size and zeta potential of EPLC with the optimized formulation were 246.1 nm and −26.94 mV, respectively. The EVO and phospholipids in the EPLC were associated with non-covalent interactions. The solubility of EPLC in water and the dissolution rate of EPLC in phosphate-buffered solution (pH 6.8) were substantially enhanced. The plasma EVO concentration-time curves of EPLC and free EVO were both in accordance with the two-compartment model. The peak concentration and AUC_0−∞ of EPLC were increased, and the relative bioavailability was significantly increased to 218.82 % compared with that of EVO.KEY WORDS: bioavailability, evodiamine, phospholipid complex, process optimization     

Food Matrix Effects on Nutraceutical Bioavailability: Impact of Protein on Curcumin Bioaccessibility and Transformation in Nanoemulsion Delivery Systems and Excipient Nanoemulsions

Powdered curcumin was either dissolved in the lipid phase of a nanoemulsion delivery system or it was directly mixed with an excipient nanoemulsion. The influence of thermal treatment (30 or 90 °C) and protein addition (caseinate) on the bioaccessibility and transformation of curcumin was then investigated using a simulated gastrointestinal tract (GIT) model: mouth; stomach; small intestine. Curcumin solubility was high in nanoemulsion delivery systems exposed to both thermal treatments because it was already present in the lipid phase. Conversely, curcumin solubility of a powder mixed with an excipient nanoemulsion was appreciably lower when exposed to 30 °C than 90 °C. This effect was attributed to the greater transfer of curcumin to the lipid phase of the excipient nanoemulsions at elevated temperatures. For the heated samples, the bioaccessibility and transformation of curcumin was not greatly affected by original curcumin location or protein addition. However, curcumin bioaccessibility was appreciably higher in the presence of nanoemulsion lipid droplets than in their absence, which was attributed to an increase in the solubilization capacity of the mixed micelle phase. This study provides some useful information for improving the design of functional foods to improve the oral bioavailability profile of lipophilic nutraceuticals.     

A Novel Approach to Evaluating the Iron and Folate Status of Women of Reproductive Age in Uzbekistan after 3 Years of Flour Fortification with Micronutrients

Background

The Uzbekistan 1996 Demographic Health Survey reported 60.4% of women of reproductive age (WRA) had low hemoglobin concentrations (<120 g/L), and anemia was an important public health problem. Fortification of wheat flour was identified as an appropriate intervention to address anemia due to the ubiquitous consumption of wheat flour. A National Flour Fortification Program (NFFP) was implemented in 2005.

Methodology/Principal Findings

After 3-years of the NFFP, a national survey using large country-lot quality assurance sampling was carried out to assess iron, folate, hemoglobin and inflammation status of WRA; the coverage and knowledge of the fortified first grade UzDonMakhsulot (UDM) flour/grey loaf program; and consumption habits of women to investigate the dietary factors associated with anemia. Estimated anemia prevalence was 34.4% (95% CI: 32.0, 36.7), iron depletion 47.5% (95% CI: 45.1, 49.9) and folate deficiency 28.8% (95% CI: 26.8, 30.8); the effect of inflammation was minimal (4% with CRP >5 mg/L). Severe anemia was more prevalent among folate deficient than iron depleted WRA. Presence of UDM first grade flour or the grey loaf was reported in 71.3% of households. Among WRA, 32.1% were aware of UDM fortification; only 3.7% mentioned the benefits of fortification and 12.5% understood causes of anemia. Consumption of heme iron-containing food (91%) and iron absorption enhancers (97%) was high, as was the consumption of iron absorption inhibitors (95%).

Conclusions/Significance

The NFFP coincided with a substantial decline in the prevalence of anemia. Folate deficiency was a stronger predictor of severe anemia than iron depletion. However, the prevalence of iron depletion was high, suggesting that women are not eating enough iron or iron absorption is inhibited. Fortified products were prevalent throughout Uzbekistan, though UDM flour must be adequately fortified and monitored in the future. Knowledge of fortification and anemia was low, suggesting consumer education should be prioritized.     

Gluconate catabolism in cowpea rhizobia: evidence for a ketogluconate pathway

Enzymatic and radiorespirometric analysis of several strains of cowpea rhizobia revealed the presence of key enzymes of the Entner-Doudoroff (ED) pathway with the operation of the hexose cycle for the dissimilation of gluconate. These bacteria lack the oxidative pentose phosphate (PP) pathway when grown on gluconate. Gluconate-grown cells possessed an operational tricarboxylic acid (TAC) cycle. Enzymes of an ancillary pathway, the ketogluconate (KG) pathway for gluconate catabolism were detected. The presence of this pathway was confirmed by techniques of thin-layer chromatography and radiorespirometry.Abbreviations ED Entner Doudoroff - PP pentose phosphate - EMP Embden-Meyerhof-Parnas - KG ketogluconate - TCA tricarboxylic acid - DKG diketogluconate - PFK phosphofructokinase     

Oxidation of Ferrous Iron by Rice (Oryza sativa L.) Roots: a Mechanism for Waterlogging Tolerance?

During an investigation of the resistance of rice (Oryza salivaL.) to ferrous iron toxicity in waterlogged soil, rice plantswere grown in an oxygen-free agar medium containing known amountsof ferrous iron. Roots grown in this way deposited ferric ironon their surface in the same manner as those grown in waterloggedsoil. Specimen roots were studied anatomically with the lightmicroscope, and with the transmission electron microscope. Analysesof deposits within the roots were carried out using the electronmicroscope and electron probe analysis. Their distribution isdescribed and it is suggested that gaseous oxygen, diffusingthrough cortical air spaces from the aerial part of the plant,is responsible for oxidation and precipitation of iron beforeit reaches the plant's conducting tissues, thereby preventingthe uptake of toxic quantities.     

Oligomerization of Glycine and Alanine Catalyzed by Iron Oxides: Implications for Prebiotic Chemistry

Iron oxide minerals are probable constituents of the sediments present in geothermal regions of the primitive earth. They might have adsorbed different organic monomers (amino acids, nucleotides etc.) and catalyzed polymerization processes leading to the formation of the first living cell. In the present work we tested the catalytic activity of three forms of iron oxides (Goethite, Akaganeite and Hematite) in the intermolecular condensation of each of the amino acids glycine and L-alanine. The effect of zinc oxide and titanium dioxide on the oligomerization has also been studied. Oligomerization studies were performed for 35 days at three different temperatures 50, 90 and 120°C without applying drying/wetting cycling. The products formed were characterized by HPLC and ESI-MS techniques. All three forms of iron oxides catalyzed peptide bond formation (23.2% of gly2 and 10.65% of ala2). The reaction was monitored every 7 days. Formation of peptides was observed to start after 7 days at 50°C. Maximum yield of peptides was found after 35 days at 90°C. Reaction at 120°C favors formation of diketopiperazine derivatives. It is also important to note that after 35 days of reaction, goethite produced dimer and trimer with the highest yield among the oxides tested. We suggest that the activity of goethite could probably be due to its high surface area and surface acidity.     

水稻耐亚铁毒QTLs的定位

亚铁毒是潜育性水稻土中限制水稻产量的主要因子。利用龙杂8503／IR64的F2和等价的F3群体,在营养液中培养来定位耐亚铁毒的QTLs。通过构建101SSR标记的遗传连锁图谱来确定耐亚铁毒QTLs的位置和特性。借助叶片棕色斑点指数、株高和最大根长3个性状,利用营养液在水稻苗期来评价F2单株、F3群体和亲本龙杂8503、IR64,共检测到叶片棕色斑点指数、株高和最大根长的QTLs20个,分布在水稻的10条染色体上,表明这些性状受多基因控制。控制叶片棕色斑点指数的QTLs分别定位在第1染色体的RM315-RM212、第2染色体的RM6-RM240和第4染色体的RM252-RM451之间。与前人的研究结果比较发现：1）位于第4染色体RM252-RM451之间的控制叶片棕色斑点指数的QTL与水稻功能图谱上控制叶绿素含量减少的QTL的位置一致。另一个位于第1染色体的RM315-RM212之间的控制叶片棕色斑点指数的QTL与水稻功能图谱上位于C178-R2635之间控制叶绿素含量的QTL连锁。2）位于第2染色体RM6-RM240之间的第3个控制叶片棕色斑点指数的QTL与位于RZ58-CD0686的控制钾吸收的QTL连锁。     

Microbial Metabolism of Benzene and the Oxidation of Ferrous Iron under Anaerobic Conditions: Implications for Bioremediation

Benzene and toluene were biodegraded when chelated Fe(III) served as the terminal electron acceptor in aquifer sediments contaminated by a petroleum refinery. Benzene biodegradation ceased when Fe(III) was depleted but resumed upon reamendment. Microorganisms from the same sediments degraded toluene, but not benzene, under nitrate reducing conditions. However, the anaerobic oxidation of Fe(II) to Fe(III) was also observed in toluene-degrading incubations. Fe(II) oxidation was dependent on the presence of nitrate and enhanced when organic electron donors were provided. Microbial nitrate-linked Fe(II) oxidation was also documented in other petroleum-contaminated aquifer sediments, sludge from an oil–water separator, a landfill leachate-impacted aquifer and a garden soil. These observations suggest that some of the reported effects of nitrate on hydrocarbon biodegradation may be indirect through the reoxidation of Fe(II).     

Sequence Analysis of the GntII (Subsidiary) System for Gluconate Metabolism Reveals a Novel Pathway for l-Idonic Acid Catabolism in Escherichia coli

The presence of two systems in Escherichia coli for gluconate transport and phosphorylation is puzzling. The main system, GntI, is well characterized, while the subsidiary system, GntII, is poorly understood. Genomic sequence analysis of the region known to contain genes of the GntII system led to a hypothesis which was tested biochemically and confirmed: the GntII system encodes a pathway for catabolism of l-idonic acid in which d-gluconate is an intermediate. The genes have been named accordingly: the idnK gene, encoding a thermosensitive gluconate kinase, is monocistronic and transcribed divergently from the idnD-idnO-idnT-idnR operon, which encodes l-idonate 5-dehydrogenase, 5-keto-d-gluconate 5-reductase, an l-idonate transporter, and an l-idonate regulatory protein, respectively. The metabolic sequence is as follows: IdnT allows uptake of l-idonate; IdnD catalyzes a reversible oxidation of l-idonate to form 5-ketogluconate; IdnO catalyzes a reversible reduction of 5-ketogluconate to form d-gluconate; IdnK catalyzes an ATP-dependent phosphorylation of d-gluconate to form 6-phosphogluconate, which is metabolized further via the Entner-Doudoroff pathway; and IdnR appears to act as a positive regulator of the IdnR regulon, with l-idonate or 5-ketogluconate serving as the true inducer of the pathway. The l-idonate 5-dehydrogenase and 5-keto-d-gluconate 5-reductase reactions were characterized both chemically and biochemically by using crude cell extracts, and it was firmly established that these two enzymes allow for the redox-coupled interconversion of l-idonate and d-gluconate via the intermediate 5-ketogluconate. E. coli K-12 strains are able to utilize l-idonate as the sole carbon and energy source, and as predicted, the ability of idnD, idnK, idnR, and edd mutants to grow on l-idonate is altered.In Escherichia coli, the Entner-Doudoroff (ED) pathway serves as a metabolic “funnel” receiving intermediates formed by catabolism of several sugar acids (17). Hexuronic acids undergo rearrangement in the inducible Ashwell pathways (1) to form 2-keto-3-deoxygluconate, which is then phosphorylated to produce 2-keto-3-deoxy-6-phosphogluconate (KDPG). KDPG is cleaved by KDPG aldolase, encoded by eda, providing for entry of carbon into glycolysis. The other enzyme of the ED pathway is 6-phosphogluconate dehydratase, encoded by edd, which is induced only for catabolism of gluconate and also forms KDPG, the key intermediate of the ED pathway (7). Long considered to be of more significance than is readily obvious (9), the finding that eda and edd eda double mutants are unable to colonize the mouse large intestine underscores the possible ecological importance of ED metabolism (32). The implication from these colonization studies is that colonic mucus, which contains several sugar acids, may serve as an important source of nutrients for E. coli in the gut.Also participating in gluconate catabolism are several gluconate transporters and two gluconate kinases which appear, based upon their regulation, to comprise two distinct systems (2, 13). The GntI (main) system consists of gntT, gntU, and gntK, which code for high- and low-affinity gluconate transporters and a thermoresistant gluconate kinase, respectively (23–25, 33). Expression of the GntR regulon, that is, GntI together with the edd-eda operon, is negatively controlled by the gntR gene product. The GntII (subsidiary) system is comprised of a thermosensitive gluconate kinase and a gluconate transporter which function for gluconate catabolism in the absence of the GntI system (2, 11, 13, 22). It appears that the subsidiary gluconate transporter, which has an apparent K_m for gluconate of 60 μM (23), is encoded by a gene (idnT) which is adjacent to the gene encoding the thermosensitive gluconokinase (idnK) at 96.8 min.The DNA sequence of the GntII system genes, located at 4492 kb on the genome, was revealed by the E. coli Genome Project (5, 6). If the GntII system had evolved as a subsidiary pathway for gluconate catabolism, one would expect it to contain only a gluconate transporter and gluconate kinase. However, in addition to the divergent idnK and idnT genes, this region also encodes two “dehydrogenase-like” enzymes. The similarity of idnO to gno of Gluconobacter oxydans, which encodes d-gluconate:NADP 5-oxidoreductase (GNO) (15), led to the testing of ketogluconates as enzyme substrates for the two newly identified dehydrogenases. A process of deductive reasoning and biochemical experiments led to the conclusion that the GntII system in fact comprises a novel metabolic pathway for catabolism of l-idonic acid, in which gluconate is a key intermediate. Accordingly, the genes involved in l-idonate metabolism have been given the designation idn (see Table ​Table11 for gene nomenclature).

TABLE 1

Gene and enzyme nomenclature^a

Bioavailability of Iron in the Regional Basic Diet (RBD) with Dietary Supplement in Brazil

The consumption of the regional basic diet (RBD) determines a state of malnutrition found in the low-income population of Northeastern Brazil. A dietary supplement known as multimixture has been used as an alternative source of iron in food for the prevention and/or treatment of anemia and for the recovery from malnutrition. The purpose of the present work was to evaluate the bioavailability of iron in the RBD supplemented with multimixture in iron-depleted and non-depleted Wistar rats. To produce iron depletion in the animals, pretest depletion diets without iron and the pretest control diet based on the AIN-93 diet were used for 8 weeks. This phase was followed by the test diets: control, AIN-93 extrinsically labeled with ⁵⁹FeCl₃; RBD, containing carioca beans intrinsically labeled with ⁵⁹Fe; and RBDMM, RBD plus multimixture, supplied in a single meal. Hemoglobin concentration, weight gain, and dietary intake were determined in the pretest phase. Iron bioavailability was determined by the determination of total-body radiation in the animals for 7 days, using a solid scintillation detector. The hemoglobin concentration, weight gain, and dietary intake were greater in the non-depleted animals than in the iron-depleted ones. The iron bioavailability of the diets did not differ significantly. It was concluded that the multimixture did not affect the bioavailability of Fe contained in the beans of the RBD.     

Comparison of a Modified Hemoglobin Regeneration Efficiency Method with a Slope-Ratio Assay in Measuring Relative Bioavailability of Cocoa Powder Iron Using Rats

The slope-ratio assay is being used as a gold standard for determining iron bioavailability in foods. We compared the modified hemoglobin (Hb) regeneration efficiency (HRE) method (Yokoi K, Konomi A, & Otagi M (2009) Br J Nutr 102: 215-220) with the slope-ratio assay for measurement of iron bioavailability. The relative bioavailability of iron in cocoa powder was measured by both methods using ferric citrate as a control (i.e., 1.00). In the slope-ratio assay, thirty-two 4-week-old male F/344?N rats were depleted in iron stores for 28?days, and then eight groups of four rats each were repleted for 25?days using graded levels of dietary ferric citrate or the cocoa powder. The slope for the cocoa powder 1.720?g Hb/L/(mg Fe/kg) was 0.99 that of ferric citrate 1.727?g Hb/L/(mg Fe/kg). On the other hand, the HRE value of the cocoa powder was 0.96 that of ferric citrate, based on the previous report. The relative iron bioavailabilities measured by both methods agreed, indicating that the modified HRE method is compatible with the slope-ratio assay in measuring the bioavailability of iron in foods.     

Prion Protein Modulates Cellular Iron Uptake: A Novel Function with Implications for Prion Disease Pathogenesis

Converging evidence leaves little doubt that a change in the conformation of prion protein (PrP^C) from a mainly α-helical to a β-sheet rich PrP-scrapie (PrP^Sc) form is the main event responsible for prion disease associated neurotoxicity. However, neither the mechanism of toxicity by PrP^Sc, nor the normal function of PrP^C is entirely clear. Recent reports suggest that imbalance of iron homeostasis is a common feature of prion infected cells and mouse models, implicating redox-iron in prion disease pathogenesis. In this report, we provide evidence that PrP^C mediates cellular iron uptake and transport, and mutant PrP forms alter cellular iron levels differentially. Using human neuroblastoma cells as models, we demonstrate that over-expression of PrP^C increases intra-cellular iron relative to non-transfected controls as indicated by an increase in total cellular iron, the cellular labile iron pool (LIP), and iron content of ferritin. As a result, the levels of iron uptake proteins transferrin (Tf) and transferrin receptor (TfR) are decreased, and expression of iron storage protein ferritin is increased. The positive effect of PrP^C on ferritin iron content is enhanced by stimulating PrP^C endocytosis, and reversed by cross-linking PrP^C on the plasma membrane. Expression of mutant PrP forms lacking the octapeptide-repeats, the membrane anchor, or carrying the pathogenic mutation PrP^102L decreases ferritin iron content significantly relative to PrP^C expressing cells, but the effect on cellular LIP and levels of Tf, TfR, and ferritin is complex, varying with the mutation. Neither PrP^C nor the mutant PrP forms influence the rate or amount of iron released into the medium, suggesting a functional role for PrP^C in cellular iron uptake and transport to ferritin, and dysfunction of PrP^C as a significant contributing factor of brain iron imbalance in prion disorders.     

Accumulation of Methylglyoxal in a Mutant of Escherichia coli Constitutive for Gluconate Catabolism

A culture of a mutant of Escherichia coli, derepressed for gluconate catabolism, is killed by the addition of gluconate to the culture. The product responsible for this bactericidal effect was identified as methylglyoxal. Two types of mutants resistant to gluconate were isolated. One of them showed increased activity of glyoxalase I.     

生血宝合剂联合琥珀酸亚铁片治疗妊娠期缺铁性贫血的疗效及对铁代谢指标和妊娠结局的影响

摘要 目的：探讨妊娠期缺铁性贫血（IDA）患者经生血宝合剂联合琥珀酸亚铁片治疗后,患者疗效、妊娠结局情况以及铁代谢指标变化情况。方法：选择2016年6月~2021年4月期间在我院接受治疗的妊娠期IDA患者100例。根据信封抽签法将患者分为对照组和研究组,各为50例。对照组患者接受琥珀酸亚铁片治疗,研究组患者接受生血宝合剂联合琥珀酸亚铁片治疗,两组患者均治疗1个月。对比两组疗效、红细胞参数、铁代谢指标、妊娠结局和不良反应发生情况。结果：研究组的临床总有效率较对照组明显更高（P>0.05）。治疗1个月后,两组血红细胞计数（RBC）、红细胞平均体积（MCV）、血红蛋白（Hb）、红细胞平均血红蛋白（MCH）均较治疗前升高,且研究组高于对照组（P<0.05）。治疗1个月后,两组血清铁（SI）、转铁蛋白饱和度（TSAT）、铁蛋白（SF）均较治疗前升高,且研究组高于对照组;转铁蛋白受体（STFR）较治疗前降低,且研究组低于对照组（P<0.05）。两组不良反应发生率对比无差异（P>0.05）。研究组剖宫产率、低体质量儿出生率低于对照组（P<0.05）。结论：生血宝合剂联合琥珀酸亚铁片治疗妊娠期IDA患者疗效显著,可促进其铁代谢恢复,提高红细胞发育程度,降低剖宫产率及低体质量儿出生率,安全可靠。