Chelators affecting iron absorption in mice

The effect of natural and synthetic chelators on iron (59Fe) absorption in mice has been studied in three different experiments using single or repeated intragastric administrations of chelator iron (59Fe) complexes of different chelator doses. The amount of 59Fe in whole animals, their excretions and also distribution of 59Fe in blood, liver, spleen and heart was measured at one, three and eight weeks following the 59Fe-chelator administrations and compared to controls which received the same amount of iron (59Fe) but no chelator. 2-Hydroxy-4-methoxypyridine-1-oxide and maltol, which form lipophilic iron complexes, were found to cause an increase of 59Fe absorption while other chelators caused a decrease either by precipitating iron eg. 2-hydroxypyridine-1-oxide or by forming non absorbable soluble iron complexes eg. desferrioxamine, mimosine, EDTA. 1,2-Dimethyl-3-hydroxypyrid-4-one caused a decrease in iron absorption at a high dose (10 mg) by comparison to the control group but it did not significantly alter iron absorption at a lower dose (2 mg). It is suggested that natural and synthetic iron chelating compounds influence the absorption of iron and some may have a use in the treatment of diseases associated with gastro-intestinal iron absorption imbalance.     

Some factors affecting the absorption of paracetamol

Blood concentration and urinary excretion data demonstrated that subjects who had ingested 1 g of paracetamol after fasting overnight absorbed the drug up to 5 times more rapidly but to the same extent as when they ingested the drug after a substantial high carbohydrate breakfast. Subjects who had ingested 1 g of paracetamol immediately before sleep at night excreted up to 36% less than when they took the drug at 8.30 a.m.     

Ascorbic acid metabolism and the clinical factors which affect tissue saturation with ascorbic acid

The factors which give rise to tissue desaturation of ascorbic acid are classified and discussed. Nutritional deprivation, normal physiological factors and metabolic factors, and pathophysiological factors may all give rise to acute and continuing ascorbic acid tissue desaturation while the factors continue to operate. Nutritional desaturation can easily be rectified by providing supplementary Vitamin C in adequate dosage. The other factors can only be rectified when the causative mechanism is arrested. Iatrogenic desaturation may be produced by aspirin and several other drugs. While causative factors excluding that of nutrition are operating, it is very difficult if not impossible to restore normal tissue values of ascorbic acid. In consequence side effects which arise from supplementary Vitamin C administration do not arise in these circumstances. The supplementary Vitamin C administration is defined as compensatory administration of Vitamin C. In healthy individuals administration of supplementary Vitamin C can be defined as (large doses). Such large doses may give rise to side effects. The mechanism by which ascorbic acid is involved in the inflammatory response is discussed.     

Molecular factors and mechanisms affecting iron and other metal excretion or absorption in health and disease: the role of natural and synthetic chelators

The maintenance of iron and other essential metal ion balance in humans is based on the presence of homeostatic mechanisms of regulatory absorption, storage, re-utilisation and excretion. There are a number of factors and mechanisms that can affect the level of iron excretion or absorption and overall body iron stores. Net iron loss due to increased iron excretion by comparison to dietary iron absorption is considered as one of the causes of iron deficiency anaemia. Body iron loss greater than normal has been shown in many other conditions. These include the increase in urinary iron excretion observed in iron loaded patients, the substantial reduction in serum ferritin and liver iron of ex-thalassaemia patients several years following bone marrow transplantation and the increase in iron excretion in normal individuals following long term sport activities. There are differences in the metabolism, mode of action, interactions with the iron pools and routes of iron excretion, of the iron chelating drugs deferiprone (L1), deferoxamine and other experimental chelators such as ICL670 in iron-loaded patients. Naturally occurring chelators and some synthetic drugs are known to bind iron and affect iron absorption and excretion. The molecular characteristics of naturally occurring or synthetic chelators can influence other aspects of iron metabolism in addition to iron absorption or excretion. Similar mechanisms and factors can affect the metabolism of other essential metals. The understanding of the mechanisms involved in iron excretion and their overall effects on body iron levels can facilitate the design of new chelators and improved therapeutic protocols for the treatment of conditions of iron and other metal metabolic imbalance and toxicity.     

Ascorbic acid: a scavenger of superoxide radical

The second order rate constant for the reaction between ascorbic acid and superoxide at pH 7.4 using the xanthine-xanthine oxidase system was estimated to be 5.4 x 10(6) M-1 sec-1. The results indicate that the efficacies of superoxide dismutase and ascorbic acid for catalyzing the decay of superoxide radical in animal tissues are similar. The significance of ascorbic acid as a scavenger of superoxide is discussed from the point of view of evolution of ascorbic acid synthesizing capacity in the terrestrial vertebrates.     

A mechanistic approach to understanding the factors affecting drug absorption: a review of fundamentals

This article provides an overview of the patient-specific and drug-specific variables that can affect drug absorption following oral product administration. The oral absorption of any chemical entity reflects a complex spectrum of events. Factors influencing product bioavailability include drug solubility, permeability, and the rate of in vivo dissolution. In this regard, the Biopharmaceutics Classification System has proven to be an important tool for predicting compounds likely to be associated with bioavailability problems. It also helps in identifying those factors that may alter the rate and extent of drug absorption. Product bioavailability can also be markedly influenced by patient attributes such as the integrity of the gastrointestinal tract, physiological status, site of drug absorption, membrane transporters, presystemic drug metabolism (intrinsic variables), and extrinsic variables such as the effect of food or concomitant medication. Through an awareness of a drug's physicochemical properties and the physiological processes affecting drug absorption, the skilled pharmaceutical scientist can develop formulations that will maximize product availability. By appreciating the potential impact of patient physiological status, phenotype, age, gender, and lifestyle, dosing regimens can be tailored to better meet the needs of the individual patient.     

Experimental factors affecting in vitro absorption of six model compounds across porcine skin

This comparative study evaluated the effect of several experimental variables on the absorption of six model [¹⁴C]-labeled compounds (caffeine, cortisone, diclofenac sodium, mannitol, salicylic acid, and testosterone) through porcine skin. Using static and flow-through diffusion cells, finite or infinite, saturated or unsaturated doses were applied in one of three vehicles: propylene glycol, water, and ethanol following a full factorial experimental design. The flux of each compound into the receptor phase, with or without bovine serum albumin (BSA), was monitored over 24 h. Levels of radioactivity were also determined in the stratum corneum by tape stripping and in the remaining skin. Apparent permeability coefficients (Kp) and dose absorbed were calculated and compared. The overall results emphasize the importance of experimental design and confirm previous findings that identified dose volume, saturation level and vehicle as the main sources of variation in the in vitro assessment of dermal absorption, whilst diffusion cell model and the presence/absence of BSA in the receptor phase had minimal effect. Although the acquired data do not directly reveal new mechanistic information on dermal absorption, the unique and complete study design has provided a suitable data source for the development of dermal absorption prediction models.     

影响血清地高辛浓度因素的调查分析

目的:探讨我院应用地高辛的现状及影响血清地高辛浓度的因素。方法:收集2005年我院861例次血清地高辛浓度数据,并采用多元回归方法分析血清地高辛浓度和年龄、性别、血清肌酐浓度、剂量等因素的关系。结果:年龄(age)、性别(sex)、血清肌酐浓度(Scr)及剂量(dose)等4因素均对血清地高辛浓度(con)有影响(P<0.05),经多元回归分析它们的关系可以表达为:con=-0.474+0.750×dose+0.154×Scr+0.128×sex+0.003×age。结论:血清地高辛浓度个体差异较大,影响血清地高辛浓度有多种因素。对于大多数患者服用地高辛的剂量不宜>0.125mg/d,如果血清肌酐值偏高,提示患者可能有肾功能减退,应该减量服用地高辛。对于女性患者更应该仔细调整剂量,以免出现地高辛中毒。     

Risk communication: factors affecting impact

The impact of risk communication depends upon a complex interaction between the characteristics of the audience, the source of the message, and its content. Audience perception of risk is influenced by demographic factors (e.g. age, gender), personality profile, past experience, and ideological orientation. It is also affected by cognitive biases (e.g. unrealistic optimism) and lay 'mental models' of the hazard. For food hazards, the important dimensions of risk are controllability, novelty and naturalness. The source must be trusted for a risk message to be effective. Trust is associated with believing the source is expert, unbiased, disinterested, and not sensationalising. To maximise impact, risk communications must have a content which triggers attention, achieves comprehension and can influence decision-making. It must be unambiguous, definitive and easily interpretable--rarely achievable particularly when risk is shrouded in scientific uncertainty. Risk messages initiate social processes of amplification and attenuation, consequently their ramifications are rarely controllable.     

Ascorbic acid in thyroidectomized rats. II) Ascorbic acid status of the storage tissues and hepatic biosynthesis of glucuronic acid

Depletion of ascorbic acid from adrenals, brain and epididymis along with loss in weight were noticed in the state of thyroidectomy. This decrease appears to be due to an effect of thyroidectomy on the membrane integrity since the membrane bound sialic acid was found to be significantly lowered in these tissues as a consequence of the elevated activity of sialidase. Thyroidectomy was also found to cause an adverse effect on the activities of hepatic UDP-glucuronyl transferase and beta-glucuronidase with no alteration in UDP-glucose dehydrogenase.     

Ascorbic acid inhibition of alpha-adrenergic receptor binding

Relatively low concentrations of ascorbic acid inhibited the binding of the alpha-1 adrenergic antagonist [125I]HEAT [DL-[beta(3-iodo-4-hydroxyphenyl)-ethyl-aminomethyl]-tetralone) in rat submandibular gland and rat aorta. However, no inhibition was observed with this ligand in several other tissues, nor with several other ligands in these tissues. The inhibition observed was dependent on the concentration of both the ascorbic acid and the tissue. Maximal inhibition of [125I]HEAT occurred in submandibular gland at 10 microM ascorbic acid with Bmax values reduced 65% and no change in affinity. Ascorbic acid had a greater effect in assays in which less tissue was used, causing a 22% decrease in binding at 46 micrograms/ml, but a 48% decrease in binding at a tissue concentration of 12 micrograms/ml. EDTA prevented the loss of binding normally seen with ascorbic acid at a tissue concentration of 17 micrograms/ml. We suggest that, if an antioxidant is thought to be necessary in an assay system, its effects be carefully examined before routine use.     

医务人员职业倦怠影响因素调查分析

目的：了解医务工作者职业倦怠情况,探讨其影响因素,为干预医务人员职业倦怠的产生寻找有效办法,同时探索在医学生中进行职业倦怠的早期干预措施。方法：自制问卷调查表,选择不同级别医院进行人员的随机调查。结果：353份有效问卷分析结果表明,医务人员发生职业倦怠和倦怠倾向的比例较高,达到62.32%。其中,医院等级越高,倦怠发生率越高;护理专业倦怠率高于医院内其他专业;工作年限在5～15年人员发生倦怠率高于其他人群;已婚者更易发生职业倦怠;不同职称人员倦怠发生率相似;男女性别出现倦怠的概率一致;不同性格人员发生职业倦怠的比例无统计差异。结论：医务工作者是职业倦怠的高发人群,并且倦怠率与医院等级正相关,护士、5～15工龄者和已婚人员为倦怠的高发群体。医疗机构应建立人文关怀体系,在医务人员群体中实施健康干预,在医学生教育中增加职业倦怠相关知识,引导个体正确评价自我,提高医务人员抗倦怠能力。     

Ascorbic acid and paraquat: Oxygen depletion with concurrent oxygen activation

Ascorbic acid and paraquat produce an efficient redox pair which will deplete oxygen from physiological buffer systems. This reaction is partially blocked by superoxide dismutase or catalase and is potentiated by the hydroxyl radical scavenger, dimethyl sulfoxide. Mitochondria isolated after incubation of rat lung slices with 1.0 mm paraquat and 10.0 mm ascorbate were unresponsive to ADP (were “uncoupled”). Also, metabolism of [1-¹⁴C]- and [6-¹⁴C]glucose was inhibited by 50% in lung slice preparations. These results suggest a synergistic interaction of ascorbate and paraquat which results in disruption of subcellular energy metabolism. Paraquat accumulation into lung slices, an active transport process of the pulmonary cell membrane, was also inhibited by the addition of ascorbate. These results suggest that the previously reported in vivo potentiation of paraquat toxicity by ascorbate may be related to either: (1) a decreased subcellular oxygen availability, or (2) the presence of activated oxygen species, or (3) both.     

Speciation analysis of iron in traditional Chinese medicine by flame atomic absorption spectrometry

In view of octanol, a long-chain alkanol, resembled as the configuration of carbohydrate and adipose in human body, the octanol-solubility and water-solubility were used to define the species of iron in medicine, to identify the lipophily and bioavailability of coordinated iron complex, and octanol-water system was adopted to study the distribution of iron in decoction of eight single medicines and compatibility of semen persicae and flos carthami in stomach and intestine. To study the effect of compatibility of medicines, the different acidity of stomach and intestine on the species of iron in phytomedicine decoction, the total concentration, octanol- and water-solubility concentration of iron in medicinal materials or decoctions under gastric and intestinal acidity, were determined, respectively, by flame atomic absorption spectrometry, analyzed and compared. The different acidity of digestive site, the different composition of medicine, and the compatibility of medicines, have greatly affected the species of iron, the pharmacological activity of coordinated iron complex in decoctions. Such factors, especially the concentration of octanol-solubility iron, could be the basis of the dosage to avoid iron overload.