Ascorbic acid: a factor concentrated in human gastric juice

1989 ◽  
Vol 76 (3) ◽  
pp. 237-241 ◽  
Author(s):  
B. J. Rathbone ◽  
A. W. Johnson ◽  
Judith I. Wyatt ◽  
J. Kelleher ◽  
R. V. Heatley ◽  
...  
Keyword(s):  
Ascorbic Acid ◽  
Gastric Juice ◽  
Chronic Gastritis ◽  
Active Form ◽  
Gastric Biopsy ◽  
The Body ◽  
Biologically Active ◽  
Human Gastric Juice ◽  
Biopsy Specimens ◽  
Inactive Form

1. Concentrations of ascorbic acid (ascorbic and dehydro-ascorbic; A+D; measured by the 2,4-dinitrophenylhydrazine method) of nearly three times those of plasma are present in gastric juice samples from patients with normal gastric histology. 2. A significant reduction in gastric juice ascorbic acid (A+D) was observed in patients with chronic gastritis. This reduction in concentration was independent of the grade of gastritis. 3. Concentrations of ascorbic acid (A+D) in gastric biopsy specimens were consistently higher in the antrum than in the body of the stomach. 4. These data demonstrate that considerable quantities of ascorbic acid (A+D) are normally ‘secreted’ into the stomach. 5. Ascorbic acid (ascorbic only; A; measured by h.p.l.c.) was present predominantly in its biologically active form in the patients with normal gastric histology. However, in patients with gastritis, independent of grade, ascorbic acid was present predominantly in its oxidized, biologically inactive form.

ATO Metabolites in APL an MM Patients Treated According to APL and MAC/DAC Schemes

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 921-921
Author(s):  
Helena Podgornik ◽  
Zdenka Slejkovec ◽  
Samo Zver ◽  
Darja Mazej ◽  
Peter Cernelc ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Arsenic Trioxide ◽  
Active Compound ◽  
Active Form ◽  
Serum Levels ◽  
The Body ◽  
Biologically Active ◽  
Atomic Fluorescence Spectrometry ◽  
Dimethylarsinic Acid ◽  
Total Arsenic

Abstract Introduction Arsenic trioxide (ATO) has been shown to be effective in the treatment of acute promyelocytic leukemia (APL) and towards multiple myeloma (MM) cells. Biologically active form of ATO is inorganic arsenic in its trivalent form (AsIII) which is metabolised in more or less active metabolites already in hours after infusion. The major arsenic excretion metabolites are methylated, namelly methylarsonic acid (MA) and dimethylarsinic acid (DMA). Despite that ATO already has an established role in APL treatment, there is still a lack of data on its metabolism especially when it is combined with other active compounds. The aim of our study was to get an insight into ATO metabolism through measurement of its metabolites in urine and total arsenic in blood during treatment according two different protocols. Patients and methods Patients (8 APL, 12 MM) were treated by ATO (administered as 2 h intravenous infusion) during the years 2004 - 2014. APL patients were previously treated according to a standard APL EORTC protocol. In three patients ATO was started immediately after an interruption of treatment due to a differentiation syndrome and in the remaining five patients ATO was started due to relapse. ATO (0.15 mg/L) was administered for i) 50 consecutive days and prolonged for 25 days (5 days/week) after 3 weeks break or for ii) 25 consecutive days repeated after one week break. Majority of 12 MM patients was heavily pretreated, relapsed or refractory. ATO (0.25 mg/kg) infusion was followed by injection of ascorbic acid (1g). Melphalan (0.1 mg/kg) or Dexamethasone (40 mg/kg) was added in MAC or DAC scheme respectively. ATO was given in cycles (4 consecutive days followed by 3 weeks of 2 applications/week). Treatment efficacy was evaluated by measurement of a monoclonal spike except for patients with Bence-Jones type of MM who were only clinically evaluated. The urine samples were taken before ATO infusion and analysed using HPLC separation combined on-line with hydride generation and atomic fluorescence spectrometry. Arsenic species As(III) and As(V) and both methylated metabolites MA and DMA were followed. Total arsenic concentrations in serum were analysed by ICP-MS. Results All APL patients have obtained a stable molecular remission. In contrast, efficacy of ATO treatment in MM patients is difficult to be evaluated due to the patients’ initial poor condition. In three MM patients effect of ATO cannot be evaluated since they deceased during the treatment. In four out of 9 remaining MM patients at least a partial remission was obtained. Differences between both groups, or better between both protocol regimens (consecutive APL or pulse DAC/MAC in MM), are also reflected in As serum levels and in the presence of ATO metabolites in urine. During the therapy the residual As serum levels in APL group were almost two times as big as those in MM group (72,33±16.79 ng/g vs. 45.13±7.2 ng/g). That means that lower daily doses of ATO preserve higher As concentrations in time than pulse therapy with higher doses. In the urine of MAC/DAC group the proportion of DMA was higher than in the patients treated according APL protocol (48.7 ± 14.6 % vs 63.2 ± 10.4%, Figure 1), while proportions of other three metabolites were lower. A higher proportion of the main active component, As(III), was present in the body of APL patients in comparison to MAC/DAC treated MM patiens (17.5 ± 7.4 % vs 8.6 ± 4.5 %; Figure 1). Differences in metabolites between both groups were statistically significant (MA: P = 0.0127; AsIII, DMA, AsIII: P < 0.0001). Figure 1 Main active compound (AsIII) and main excretion ATO metabolite (DMA) in urine of APL and MM patients. Figure 1. Main active compound (AsIII) and main excretion ATO metabolite (DMA) in urine of APL and MM patients. Conclusions APL patients receiving ATO daily reached a sort of a steady state with a peak in As(III) concentration after i.v. infusion and gradual fall of As(III) concentration until the next day’s infusion while concentrations of other metabolites remained relatively stable. MM patients received higher ATO doses in pulses so that decrease of As(III) after initial peak ended in prolonged lower As(III) levels in between infusions. Poor response to ATO treatment in few MM patients can be attributed to their pretreatment status but also to suboptimal treatment protocol. Significantly lower residual serum As levels were observed during DAC/MAC in comparison to daily treatment according to APL protocol. Lower but more frequent doses of ATO, similar to those in APL, may be more effective in MM. Disclosures Off Label Use: Arsenic trioxide, drug with known antimyeloma activity. It was used as salvage options in multiple myeloma pts., in whom all other conventional treatment options were exhausted. Those patients would be otherwise treated only in a paliative way. They all wrote informed consent after we discussed the issue with them.

scholarly journals Hydroxyl Radical Generation by the Combination of Iron and Ascorbic Acid is Greatly Attenuated but Still Significant in Human Gastric Juice.

2002 ◽  
Vol 41 (12) ◽  
pp. 1213-1214 ◽  
Author(s):  
Tomoyo KAGAWA ◽  
Genzou TAKEMURA ◽  
Xinbin Qiu ◽  
Rumi MARUYAMA ◽  
Ningyuan WANG ◽  
...  
Keyword(s):  
Ascorbic Acid ◽  
Hydroxyl Radical ◽  
Gastric Juice ◽  
Human Gastric Juice ◽  
Radical Generation

scholarly journals The Microbiome–Estrogen Connection and Breast Cancer Risk

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1642 ◽  
Author(s):  
Sheetal Parida ◽  
Dipali Sharma
Keyword(s):  
Breast Cancer ◽  
Enterohepatic Circulation ◽  
Active Form ◽  
Human Microbiome ◽  
The Body ◽  
Biologically Active ◽  
Cancer Development ◽  
Intestinal Microbes ◽  
Breast Cancer Development ◽  
Dietary Polyphenols

The microbiome is undoubtedly the second genome of the human body and has diverse roles in health and disease. However, translational progress is limited due to the vastness of the microbiome, which accounts for over 3.3 million genes, whose functions are still unclear. Numerous studies in the past decade have demonstrated how microbiome impacts various organ-specific cancers by altering the energy balance of the body, increasing adiposity, synthesizing genotoxins and small signaling molecules, and priming and regulating immune response and metabolism of indigestible dietary components, xenobiotics, and pharmaceuticals. In relation to breast cancer, one of the most prominent roles of the human microbiome is the regulation of steroid hormone metabolism since endogenous estrogens are the most important risk factor in breast cancer development especially in postmenopausal women. Intestinal microbes encode enzymes capable of deconjugating conjugated estrogen metabolites marked for excretion, pushing them back into the enterohepatic circulation in a biologically active form. In addition, the intestinal microbes also break down otherwise indigestible dietary polyphenols to synthesize estrogen-like compounds or estrogen mimics that exhibit varied estrogenic potency. The present account discusses the potential role of gastrointestinal microbiome in breast cancer development by mediating metabolism of steroid hormones and synthesis of biologically active estrogen mimics.

scholarly journals SELECTION OF AN EXTRACTANT FOR ISOLATION OF BIOLOGICALLY ACTIVE COMPOUNDS FROM A HEDYSARUM NEGLECTUM

2020 ◽  
Author(s):  
Anastasia Dmitrieva ◽  
Dyshlyuk Lubov ◽  
Fotina Natalia
Keyword(s):  
Ascorbic Acid ◽  
Human Body ◽  
The Body ◽  
Biologically Active Substances ◽  
Biologically Active ◽  
Ethanol Mixture ◽  
Industrial Enterprises ◽  
Promising Source ◽  
Active Substances ◽  
Selection Of

Global technological progress is one of the main problems of ecosystem deterioration. The high concentration of industrial enterprises contributes to the development of the region's environmental crisis and the decline in public health. An increase in the environmental pollutant contributes to the activation of oxidative stress in the human body, which plays a key role in the pathogenesis of a number of chronic diseases (cancer, diabetes, cardiovascular diseases, etc.), leading to a decrease in life expectancy and early aging of the body. To increase the adaptive abilities of the human body, it is important to use plant raw materials. A promising source of natural nutrients is the Hedysarum neglectum Ledeb. In order to obtain the extract of the forgotten kopek, the method of extraction was used at room temperature with a reverse refrigerator for 2 hours. In this study, to determine the working parameters of extraction (type of extractant, concentration of extractant), a selection of various extractive substances was selected. The efficiency of the extraction process was determined by two parameters: extractivity and yield of biologically active substances. The maximum extractivity was observed when using 50 % ethyl alcohol. To determine the working concentration of the water-ethanol mixture, the prepared extracts were analyzed for the content of flavonoids, tannins, and ascorbic acid. The maximum yield of biologically active substances (flavonoids 419.02±3.58 mg%, tannins 8.10±1.03 %, ascorbic acid 691.04±3.62 mg/kg) was observed during extraction with 50% water-ethanol mixture. The obtained results suggest that the water-ethanol extract of Hedysarum neglectum Ledeb. it is a potential source of natural biologically active substances for creating functional food products.

scholarly journals The diagnostic value of indicators of acid-forming and pepsinoguena functions of the stomach in the detection of precancerous changes of the gastric mucosa in patients with chronic gastritis

2018 ◽  
Vol 20 (4) ◽  
pp. 72-75
Author(s):  
I M Pavlovich ◽  
G A Alper ◽  
A V Gordienko
Keyword(s):  
Gastric Mucosa ◽  
Intestinal Metaplasia ◽  
Gastric Juice ◽  
Mucous Membrane ◽  
Chronic Gastritis ◽  
Chronic Atrophic Gastritis ◽  
Diagnostic Value ◽  
The Body ◽  
Significant Difference ◽  
Low Activity

It was found that in patients with chronic atrophic gastritis, low gastric secretory functions are present in the localization of atrophy in the mucous membrane of the body of the stomach with a tendency to decrease in indices as the degree of atrophy increases and are not associated with the presence of disregenerative changes in the gastric mucosa (intestinal metaplasia and dysplasia). Reduced levels of pepsin in gastric juice and reduced levels of pepsinogen in the mucous membrane of the body of the stomach reliably reflect the presence of severe atrophy of the mucous membrane of the body of the stomach. However, neither the concentration of pepsinogen in the tissues of the mucous membrane of the body of the stomach nor the level of pepsin in the gastric juice make it possible to differentiate the degree of atrophy of the gastric mucosa. The most profound disregenerative changes in gastric mucosa such as colonic metaplasia or dysplasia were detected, accordingly in 18,4 and 10,5% of patients. The presence of intestinal metaplasia or dysplasia causes a low activity of pepsinogen-pepsin. It worth noting that in case of the presence of intestinal metaplasia and dysplasia there is a significant difference between indicators of the concentration of pepsinogen-pepsin and those at patients with chronic gastritis, but without disregenerative changes of the mucous membrane. Also was found an association between the severity of disregenerative changes in the gastric mucosa and the degree of the reduction of pepsin-forming function.

scholarly journals The stomach as the target organ of celiac disease

2018 ◽  
Vol 9 (4) ◽  
pp. 64-72
Author(s):  
Valeria P. Novikova ◽  
Natalia S. Shapovalova ◽  
Maria O. Revnova ◽  
Valentina F. Melnikova ◽  
Sergey V. Lapin ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Gastric Mucosa ◽  
Histological Examination ◽  
Chronic Gastritis ◽  
The Body ◽  
Group Iii ◽  
Biopsy Specimens ◽  
Group I ◽  
Significant Difference ◽  
Group Ii

The aim of this study was to observe the features of chronic gastritis in children with celiac disease (СD). Materials and methods. 176 children with chronic gastritis (CG) aged from 3 to 16 years were examined. Group I consisted 58 child ren with CG and newly diagnosed CD not adherent to the gluten-free diet (GFD), group II consisted 49 children with CG and CD, adherent to the GFD. In the group III of comparisons were 69 children with CG and excluded CD. The exa mination included serological, morphological methods to confirm or exclude CD. The histological examination of the biopsy specimens of the gastric mucosa, the determination of antiparietal antibodies by the method of iIFR and ELISA (antibodies to Castle’s intrinsic factor and Anti-H+/K+ ATPase antibodies) were carried out. Results. Helicobacter pylori infection was diagnosed in vast majority of patients in all groups. Autoantibodies to the gastric mucosa were found in every tenth patient in groups I and III, and did not occur in group II. In group II statistically significant the etiology of gastritis remained not determined. Endoscopically the gastric mucosa in groups I and II often remained intact. Accor ding to the morphological study in groups I and II, the pathological process was more often localized in the body of the stomach, and in group III in the antrum. Autoimmune gastritis is presented in groups without a statistically significant difference. Conclusion. Chronic gastritis is a frequent co-morbid pathology in СD, and it is also not uncommon in these patients. Data of endoscopy in children, regardless of diet, does not reflect the complete picture of CG. All children with CD, regardless of compliance with GFD, are recommended to take biopsy specimens of the gastric mucosa for histological examination in order to exclude CG, and in case of detecting atrophic changes in the gastric mucosa to define the antiparietal antibodies.

scholarly journals Nanoparticle-directed and ionically forced polyphosphate coacervation: a versatile and reversible core–shell system for drug delivery

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Werner E. G. Müller ◽  
Emad Tolba ◽  
Shunfeng Wang ◽  
Meik Neufurth ◽  
Ingo Lieberwirth ◽  
...  
Keyword(s):  
Ascorbic Acid ◽  
Calcium Ions ◽  
Active Form ◽  
Biologically Active ◽  
Core Shell ◽  
Drug Encapsulation ◽  
The Core ◽  
Hydrogel Matrix ◽  
Shell Particles ◽  
Nanoparticle Core

Abstract A drug encapsulation/delivery system using a novel principle is described that is based on an intra-particle migration of calcium ions between a central Ca2+-enriched nanoparticle core and the surrounding shell compartment. The supply of Ca2+ is needed for the formation of a coacervate shell around the nanoparticles, acting as the core of drug-loadable core–shell particles, using the physiological inorganic polymer polyphosphate (polyP). This polyanion has the unique property to form, at an alkaline pH and in the presence of a stoichiometric surplus of calcium ions, water-insoluble and stabile amorphous nanoparticles. At neutral pH a coacervate, the biologically active form of the polymer, is obtained that is composed of polyP and Ca2+. The drug-loaded core–shell particles, built from the Ca–polyP core and the surrounding Ca–polyP shell, were fabricated in two successive steps. First, the formation of the nanoparticle core at pH 10 and a superstoichiometric 2:1 molar ratio between CaCl2 and Na–polyP into which dexamethasone, as a phosphate derivative, was incorporated. Second, the preparation of the coacervate shell, loaded with ascorbic acid, by exposure of the Ca–polyP core to soluble Na–polyP and L-ascorbate (calcium salt). EDX analysis revealed that during this step the Ca2+ ions required for coacervate formation migrate from the Ca–polyP core (with a high Ca:P ratio) to the shell. Electron microscopy of the particles show an electron-dense 150–200 nm sized core surrounded by a less sharply delimited electron-sparse shell. The core–shell particles exhibited strong osteogenic activity in vitro, based on the combined action of polyP and of dexamethasone and ascorbic acid, which reversibly bind to the anionic polyP via ionic Ca2+ bonds. Drug release from the particles occurs after contact with a peptide/protein-containing serum, a process which is almost complete after 10 days and accompanied by the conversion of the nanoparticles into a coacervate. Human osteosarcoma SaOS-2 cells cultivated onto or within an alginate hydrogel matrix showed increased growth/viability and mineralization when the hybrid particles containing dexamethasone and ascorbic acid were embedded in the matrix. The polyP-based core–shell particles have the potential to become a suitable, pH-responsive drug encapsulation/release system, especially for bone, cartilage and wound healing.

Amperometric microsensor for direct probing of ascorbic acid in human gastric juice

2010 ◽  
Vol 678 (2) ◽  
pp. 176-182 ◽  
Author(s):  
Emily A. Hutton ◽  
Rasa Pauliukaitė ◽  
Samo B. Hocevar ◽  
Božidar Ogorevc ◽  
Malcolm R. Smyth
Keyword(s):  
Ascorbic Acid ◽  
Gastric Juice ◽  
Human Gastric Juice
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