Bioavailability of Stabilised Ferrous Gluconate with Glycine in Fresh Cheese Matrix: a Novel Iron Compound for Food Fortification

Iron fortification of foods continues to be one of the preferred ways of improving the iron status of the population. Dairy product is a common product in the diet; therefore, it is a plausible vehicle for iron fortification. This study aims to investigate the bioavailability of ferrous gluconate stabilised with glycine (FGSG) in a fresh cheese fortified with zinc. The iron bioavailability of fresh cheese fortified with either FGSG and with or without zinc and FGSG in aqueous solution and a water solution of ferrous ascorbate (reference dose) was studied using double radio iron (⁵⁵Fe and ⁵⁹Fe) erythrocyte incorporation in 15 male subjects. All subjects presented with normal values for iron status parameters. The geometric mean of iron bioavailability for the water solution of FGSG was 38.2 %, adjusted to 40 % from reference doses (N.S.). Iron bioavailability in fresh cheese fortified with Ca and Zn was 15.4 % and was 23.1 % without Zn, adjusted to 40 % from reference doses (N.S.). The results of the present study show that the novel iron compound ferrous gluconate stabilised with glycine in a fresh cheese matrix is a good source of iron and can be used in iron fortification programmes.     

The Efficacy and Adverse Reaction of Bleeding of Clopidogrel plus Aspirin as Compared to Aspirin Alone after Stroke or TIA: A Systematic Review

Background and Purpose

Given the high risk of stroke after TIA (transient ischemia attack) or stroke and the adverse reaction of bleeding of antiplatelets, we undertook a meta-analysis, reviewed randomized controlled trials (RCTs) comparing aspirin plus clopidogrel with aspirin alone to determine the efficacy and adverse reaction of bleeding of the two protocols in the prevention of stroke.

Methods

We analyzed the incidences of stroke, bleeding and severe bleeding by using fixed-effect model or random-effect model on the basis of the result of heterogeneity test.

Results

Five qualified RCTs satisfied the inclusion criteria. We found that treatment with aspirin plus clopidogrel was associated with lower incidence of stroke (Risk Ratio (RR), 0.66, 95% confidence interval (CI), 0.47 to 0.93), higher incidence of bleeding (RR, 1.75, 95% CI, 1.48 to 2.05) as compared with aspirin-alone treatment. In terms of severe bleeding, no statistical difference existed between them (RR, 2.21, 95% CI, 0.25 to 19.52).

Conclusion

The combined use of aspirin and clopidogrel is more effective than aspirin alone for patients with previous TIA or stroke for the prevention of stroke, with risk of bleeding being higher. No statistical difference was found in severe bleeding between the two treatment protocols.     

Clopidogrel and Aspirin versus Aspirin Alone for Stroke Prevention: A Meta-Analysis

Background and Purpose

Antiplatelet therapy is widely used for the primary or secondary prevention of stroke. Drugs like clopidogrel have emerged as alternatives for traditional antiplatelet therapy, and dual therapy with clopidogrel and aspirin is of particular interest. We conducted this meta-analysis to systematically review studies about dual therapy comparing monotherapy with aspirin alone.

Methods

Randomized controlled trials were searched in PubMed (1966-May, 2015), EMBASE (1947-May, 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (1948-May, 2015), WHO International Clinical Trial (ICTRP) (2004-May, 2015), China Biology Medicine disc (CBM disc) (1978-May, 2015) and were included into the final analysis according to the definite inclusion criteria mentioned in the study selection section. Risk ratio (RR) was pooled with 95% confidence interval (CI) for dichotomous data. The heterogeneity was considered significant if the χ² test was significant (P value < 0.10) or the I² > 50.00%. Subgroup analyses were carried out on the long and short time periods, the race and region.

Results

We included 5 studies involving 24,084 patients. A pooled analysis showed that dual therapy with clopidogrel and aspirin had a lower stroke incidence than monotherapy in both the short term and long term (RR = 0.69, 95% CI: 0.59–0.82, P <0.05; RR = 0.84, 95% CI: 0.72–0.98, P = 0.03, respectively). With regard to safety, dual therapy had a higher risk of bleeding than monotherapy for both periods (RR = 1.51, 95% CI: 1.03–2.23, P = 0.04; RR = 1.54, 95% CI: 1.32–1.79, P<0.05, respectively).

Conclusions

Dual therapy with clopidogrel and aspirin could be a preferable choice to prevent stroke in patients who have had a previous stroke or transient ischemic attack, as well as those who are at high risk for stroke. And the effect of dual therapy seems to be more obvious for short-term. However, it is associated with a higher risk of bleeding.     

Aspirin interaction with ribonuclease a

Aspirin is an anti-inflammatory drug and a main source of protein acetylation that can alter enzymatic activity and protein functions. Ribonuclease A (RNase A) with several high-affinity binding sites is a possible target for many organic and inorganic molecules (Leonidas at al., [2003] Protein Sci. 12, 2559–2574). This study was designed to examine the interaction of aspirin with RNase A at physiologic conditions. Reaction mixtures of constant protein concentration (3 mM) and different aspirin contents (0.0002–2 mM) are studied by ultraviolet-visible, Fourier transform infrared, and circular dichroism spectroscopic methods to determine the drug binding mode, the drug-binding constant, and the effects of drug complexation on the protein conformation in aqueous solution. Spectroscopic results showed one major binding for the aspirin-RNase complexes with overall binding constant of K=3.57×10⁴ M ⁻¹. Minor reductions in the protein α-helix from 15.5 to 14.1% (circular dichroism) using CDPro program and 26 to 21% (infrared) were observed on aspirin interaction. The changes are indicative of some degree of protein unfolding on drug complexation.     

A Novel Reaction of Dehydroaltenusin with Diazomethane

Several fluorine- and bromine-containing BHC analogs having the γ-configuration were synthesized.     

Control of Gluconate Utilization in Sinorhizobium meliloti

The Sinorhizobium meliloti megaplasmid pSymA has previously been implicated in gluconate utilization. We report a locus on pSymA encoding a putative tripartite ATP-independent periplasmic (TRAP) transporter that is required for gluconate utilization. The expression of this locus is negatively regulated by a GntR family regulator encoded adjacent to the transporter operon.     

Ferrous Iron Treatment of Soils Contaminated with Arsenic-Containing Wood-Preserving Solution

This article discusses the results of efforts to reclaim As-contaminated soil from a former timber-treating plant. The study site, commonly referred to as the Rocker Timber Framing site, is located along Silver Bow Creek approximately 7 miles west of the Butte Mining District, MT, USA. The plant operations resulted in contamination of the soils with a highly caustic solution containing 5% As (III). Contaminated soil resulted in the groundwater plumes that contained up to 25?mg L^?1 As, with As (V) being the predominant species. The objective of this study was to evaluate the effectiveness of Fe (II) treatment for remediation of As-contaminated soils. Laboratory-treatability studies were conducted on samples of saturated zone (AS1) and va-dose zone (AV1) soils. The AS1 soil was a mixture of coarse alluvium and potentially some mill tailings from adjacent mining operations. The AV1 soil consisted primarily of fill, including soil, construction debris, and timber fragments. Initial concentrations of total As in AS1 and AV1 soils were 683 and 4814?µg kg^?1, respectively. Water-soluble As concentrations were 15.4 and 554?µg L^?1, respectively, in a 20:1 solution to soil extract. Batch equilibration were performed by placing 10?g of soil into 20 vessels and adding increasing amounts of FeSO₄.7H₂O. Amendment increments were made as multiples of molar ratios of total As present in each soil. Treatability studies were run with and without a pH buffer of CaCO₃ (added at a 2:1 molar ratio to the FeSO₄.7H₂O treatment). Solution concentrations of As in the AS1 and AV1 soils (without CaCO₃) decreased from 554 to 15.4?µ L^?1 and 3802 to 0.64?µ L^?1, respectively, as the Fe:As molar ratios increased from 0 to 2, whereas for the AS1 soil the solution As concentration increased at the Fe:As molar ratios >2 and reverse trend was observed for the AV1 soils. The decrease in As solution concentration for the AS1 soil is attributable to the dramatic decrease in soil pH with increasing Fe:As molar ratios. In the case of soils treated with CaCO₃, the solution concentrations decreased from 564 to 0.65?µg L^?1 and 3790 to 0.79?µg L^?1 for the AS1 and AV1 soils, respectively,as the Fe:As molar ratios increased from 0 to 50. Generally, in both the soils, the CaCO₃-treated soil contained significantly more solution As compared with the non-CaCO₃-treated soil at the comparable Fe:As molar ratios. This is attributable to higher solution pH on CaCO₃ treatment. Our rapid engineering study indicates that treating both the soils with Fe:As molar ratio of 2 lowered the As water quality limit to <50?µL^?1, whereas treating the AS1 and AV1 soils with Fe:As molar ratio of 2 and 3, respectively, lowered the As water quality limit to ≤15?µg L^?1. The concentrations of the Cu and Zn were below the instrument detection limits for the AS1 and AV1 soils without CaCO₃ treatment. Sequential extraction of Fe-treated soils illustrated that As was relatively stable. Less than 1% of the As was extractable using a modified TCLP approach and <70% of the As was extractable using a harsh acid modified hydroxylamine hydrochloride extraction.     

Gluconate accumulation and enzyme activities with extremely nitrogen-limited surface cultures of Aspergillus niger

Batch cultures of Aspergillus niger grown from conidia on a medium with high C/N ratio accumulated gluconate from glucose with a yield of 57%. During almost the whole time of accumulation there was no net synthesis of total protein in the mycelium but the activity per flask and the specific activity of glucose oxidase (EC 1.1.3.4) in mycelial extracts increased whereas both values decreased for glucose dehydrogenase (EC 1.1.99.10) gluconate 6-phosphatase (cf. EC 3.1.3.1, 3.1.3.2), gluconokinase (EC 2.7.1.12), glucose 6-phosphate and phosphogluconate dehydrogenases (EC 1.1.1.49, EC 1.1.1.44), phosphoglucomutase (EC 2.7.5.1), and most enzymes of the Embden-Meyerhof pathway and the tricarboxylic acid cycle. Gluconate dehydratase (EC 4.2.1.39), gluconate dehydrogenase (EC 1.1.99.3) and enzymes of the Entner-Doudoroff pathway could not be detected. By cycloheximide the increase of glucose oxidase activity was inhibited. It is concluded that the high yield of gluconate was due mainly to the net (de novo) synthesis of glucose oxidase which occurred during protein turnover after the exhaustion of the nitrogen source, and which was not accompanied by a net synthesis of the other enzymes investigated. Some gluconate may also have been formed by hydrolytic cleavage of gluconate 6-phosphate.Abbreviations GOD glucose oxidase - GD glucose dehydrogenase - PP pentose phosphate - EM Embden-Meyerhof - TCA tricarboxylic acid     

Gluconate Metabolism by a Thiamine-requiring Species of Corynebacterium

A thiamine-requiring strain of Corynebacterium was found to accumulate a ketopentose extracellularly from gluconate. The ketopentose was isolated from the culture medium and identified as d-ribulose. The accumulation of d-ribulose was significantly influenced by the concentration of thiamine in the medium. The maximum yield of d-ribulose was obtained at a thiamine concentration of 10 μg per liter, whereas good growth was favored at thiamine concentrations greater than 50 μg per liter. The accumulation of d-ribulose reached the concentration of 9.5 mg per ml after cessation of cell growth in shake culture at 30°C in a medium containing 6% potassium gluconate as a carbon source.     

Treatment of Rheumatoid Arthritis with Fenoprofen: Comparison with Aspirin

Fenoprofen, a compound with analgesic, anti-inflammatory, and antipyretic properties in animals, has been compared with placebo in a double-blind cross-over trial in 60 patients with rheumatoid arthritis. There was a statistically highly significant reduction in pain, duration of morning stiffness, analgesic requirements, and articular index, with increase in grip strength. There was no significant reduction in joint size or temperature. In a subsequent double-blind group-comparative study fenoprofen proved to be as effective as aspirin in relieving the symptoms of rheumatoid arthritis, with strikingly fewer side effects. Almost half of the patients taking aspirin were unable to tolerate the drug in adequate dosage for six months. The remainder were able to take on average only 4 g daily, and at this dose almost half still complained of tinnitus and deafness.Fenoprofen is likely to be useful for patients who cannot tolerate aspirin and other more toxic anti-inflammatory drugs or whose disease is not of sufficient severity to justify their use.     

酪酸梭菌活菌散联合葡萄糖酸锌治疗儿童急性腹泻的疗效观察

目的探讨酪酸梭菌活菌散联合葡萄糖酸锌治疗儿童急性腹泻的疗效。方法选取急性腹泻患儿76例,随机分为观察组和对照组各38例。两组患儿均予以调整饮食、口服或静脉补液和纠正水电解质酸碱失衡紊乱等常规治疗。观察组患儿予以酪酸梭菌活菌散和葡萄糖酸锌联合治疗,对照组患儿予以单纯酪酸梭菌活菌散治疗。观察两组患儿治疗后主要症状和体征改善的时间,并比较其临床疗效及治疗后3个月内腹泻的复发率。结果观察组患儿治疗后的止泻、呕吐、腹痛和粪常规等恢复正常时间均明显短于对照组（P〈0.05）;同时治疗3 d后,观察组患儿临床总有效率为94.74%,明显高于对照组的78.95%（χ2=4.15,P〈0.05）。两组患儿治疗后随访3个月,其中观察组和对照组分别腹泻复发5例（13.16%）和13例（34.21%）,观察组腹泻的复发率明显低于对照组（χ2=4.66,P〈0.05）。结论酪酸梭菌活菌散联合葡萄糖酸锌治疗儿童急性腹泻的疗效较肯定,能明显改善患儿腹泻症状,缩短腹泻病程,并能减少腹泻的复发。     

环氧合酶基因多态性与阿司匹林抵抗的关系

目的:研究缺血性脑卒中患者阿司匹林抵抗与血小板环氧合酶(COX)单核苷酸基因多态性(SNP)的相关性.方法:169位缺血性脑卒中患者服用阿司匹林100mg/d至少7d,根据血栓弹力图(TEG)检测结果分为阿司匹林敏感(AS)组和非阿司匹林敏感(NAS)组,并采用PCR产物直接测序分析法对患者的COX-1(-1676A＞G)、COX-2(-765G＞C)基因的单核苷酸多态性进行分析.结果:根据TEG检测结果,非阿司匹林敏感(NAS)组66例,阿司匹林敏感(AS)组103例.两组患者间COX-1基因-1676A＞G SNP位点的基因型和等位基因频率分布差异具有统计学意义(P=0.016和P=0.008),特别是其等位基因频率分布具有显著差异.两组患者间COX-2基因-765G＞C SNP位点的基因型和等位基因频率分布差异无统计学意义(P=0.084和P=0.090).结论:COX-1基因-1676A＞G位点多态性可能与缺血性脑卒中患者患者阿司匹林抵抗的发生相关,COX-2基因-765G＞C位点多态性可能与阿司匹林抵抗的发生无关.     

Aspirin tolerance in individuals with aspirin-induced urticaria-edematous lesions

The study involved 22 individuals with aspirin-produced urticaria-edematous skin lesions. Hypersensitivity to aspirin was established with anamnesis showing such lesions on aspirin intake and oral test with aspirin. Threshold, provocative dose of aspirin was determined in all patients at the beginning of the study. Moreover, threshold provocative indomethacin dose was additionally determined in 12 patients. Tolerance to aspirin was produced by the oral administration of aspirin in increasing doses upto total dose 600 mg at a 24-hour intervals. Twelve patients were given 25 mg of indomethacin after 24 hours, and 50 mg of this drug after 48 hours. The patients tolerated indomethacin well during aspirin tolerance stage. The authors suggest that both urticaria-edematous and bronchial type of aspirin hypersensitivity are of the same pathogenetic origin.