scholarly journals Folate absorption from folate-fortified and processed foods using a human ileostomy model

2006 ◽  
Vol 95 (1) ◽  
pp. 181-187 ◽  
Author(s):  
Cornelia M. Witthöft ◽  
Karin Arkbåge ◽  
Madelene Johansson ◽  
Eva Lundin ◽  
Gerd Berglund ◽  
...  
Keyword(s):  
Single Dose ◽  
Folic Acid ◽  
Dairy Products ◽  
Kinetic Modelling ◽  
Fermented Milk ◽  
Processed Foods ◽  
Dietary Requirements ◽  
Folate Binding Proteins ◽  
Plasma Concentration Curve

Data on folate absorption from food from validated human studies using physiological folate doses are still needed to estimate dietary requirements and to formulate recommendations. The aim of the present work was to study the effects from fortified and processed foods on folate absorption in ileostomy volunteers (n 9) using the area under the plasma concentration curve (AUC) and kinetic modelling. Using a standardized single-dose protocol, dairy products fortified with a candidate fortificant (6S)-5-methyltetrahydrofolate ((6S)-5-CH3-H4folate), folic acid-fortified bread and a dessert crème containing natural yeast folate polyglutamates were compared with folate supplements. Absorbed folate was estimated by AUC and a kinetic model, and non-absorbed folate by ileostomal folate excretion. Median apparent absorption from test foods ranged from 55 to 86%. Added folate-binding proteins (FBP) significantly reduced folate absorption from dairy products, as in the absence of FBP, AUC–dose-corrected ratios were increased and ileal folate excretion decreased. After in vivo gastrointestinal passage of dairy products containing FBP, up to 43% of the ingested FBP was found in ileostomal effluent. Folate absorption was similar for (6S)-5-CH3-H4folate fortificant from fermented milk and for folic acid from fortified bread. Folic acid, ingested as food fortificant in bread, was significantly less absorbed compared with an isolated supplement. We conclude that all tested foods were suitable matrices for folate fortification. However, dairy products, fortified with the new candidate fortificant (6S)-5-CH3-H4folate, are suitable if no active FBP is present.

Bioavailability of Vitamin B12

2010 ◽  
Vol 80 (45) ◽  
pp. 330-335 ◽  
Author(s):  
Lindsay Helen Allen
Keyword(s):  
Vitamin B12 ◽  
Vitamin B12 Deficiency ◽  
The Elderly ◽  
Radioactive Isotopes ◽  
Animal Source Foods ◽  
Dietary Requirements ◽  
In Vivo Labeling ◽  
B12 Deficiency ◽  
Vitamin B12 Malabsorption

Vitamin B12 deficiency is common in people of all ages who consume a low intake of animal-source foods, including populations in developing countries. It is also prevalent among the elderly, even in wealthier countries, due to their malabsorption of B12 from food. Several methods have been applied to diagnose vitamin B12 malabsorption, including Schilling’s test, which is now used rarely, but these do not quantify percent bioavailability. Most of the information on B12 bioavailability from foods was collected 40 to 50 years ago, using radioactive isotopes of cobalt to label the corrinoid ring. The data are sparse, and the level of radioactivity required for in vivo labeling of animal tissues can be prohibitive. A newer method under development uses a low dose of radioactivity as 14C-labeled B12, with measurement of the isotope excreted in urine and feces by accelerator mass spectrometry. This test has revealed that the unabsorbed vitamin is degraded in the intestine. The percent bioavailability is inversely proportional to the dose consumed due to saturation of the active absorption process, even within the range of usual intake from foods. This has important implications for the assessment and interpretation of bioavailability values, setting dietary requirements, and interpreting relationships between intake and status of the vitamin.

scholarly journals Inhibition of Kirsten-Ras reduces fibrosis and protects against renal dysfunction in a mouse model of chronic folic acid nephropathy

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Lucy J. Newbury ◽  
Jui-Hui Wang ◽  
Gene Hung ◽  
Bruce M. Hendry ◽  
Claire C. Sharpe
Keyword(s):  
Folic Acid ◽  
Kidney Disease ◽  
Mouse Model ◽  
Renal Dysfunction ◽  
Antisense Oligonucleotides ◽  
Underlying Mechanism ◽  
Therapeutic Benefit ◽  
End Stage

Abstract Chronic Kidney Disease is a growing problem across the world and can lead to end-stage kidney disease and cardiovascular disease. Fibrosis is the underlying mechanism that leads to organ dysfunction, but as yet we have no therapeutics that can influence this process. Ras monomeric GTPases are master regulators that direct many of the cytokines known to drive fibrosis to downstream effector cascades. We have previously shown that K-Ras is a key isoform that drives fibrosis in the kidney. Here we demonstrate that K-Ras expression and activation are increased in rodent models of CKD. By knocking down expression of K-Ras using antisense oligonucleotides in a mouse model of chronic folic acid nephropathy we can reduce fibrosis by 50% and prevent the loss of renal function over 3 months. In addition, we have demonstrated in vitro and in vivo that reduction of K-Ras expression is associated with a reduction in Jag1 expression; we hypothesise this is the mechanism by which targeting K-Ras has therapeutic benefit. In conclusion, targeting K-Ras expression with antisense oligonucleotides in a mouse model of CKD prevents fibrosis and protects against renal dysfunction.

scholarly journals Influence of Camembert consumption on the composition and metabolism of intestinal microbiota: a study in human microbiota-associated rats

2004 ◽  
Vol 92 (3) ◽  
pp. 429-438 ◽  
Author(s):  
Christophe Lay ◽  
Malène Sutren ◽  
Pascale Lepercq ◽  
Catherine Juste ◽  
Lionel Rigottier-Gois ◽  
...  
Keyword(s):  
Intestinal Microbiota ◽  
Dairy Products ◽  
Basal Diet ◽  
Fermented Milk ◽  
Metabolic Characteristics ◽  
Human Microbiota ◽  
Gradient Gel Electrophoresis ◽  
Metabolic Activities ◽  
Temperature Gradient Gel Electrophoresis ◽  
Micro Organisms

The objective of the present study was to evaluate the consequence of Camembert consumption on the composition and metabolism of human intestinal microbiota. Camembert cheese was compared with milk fermented by yoghurt starters andLactobacillus caseias a probiotic reference. The experimental model was the human microbiota-associated (HM) rat. HM rats were fed a basal diet (HMB group), a diet containing Camembert made from pasteurised milk (HMCp group) or a diet containing fermented milk (HMfm group). The level of micro-organisms from dairy products was measured in faeces using cultures on a specific medium and PCR–temporal temperature gradient gel electrophoresis. The metabolic characteristics of the caecal microbiota were also studied: SCFA, NH3, glycosidase and reductase activities, and bile acid degradations. The results showed that micro-organisms from cheese comprised 105–108bacteria/g faecal sample in the HMCp group.Lactobacillusspecies from fermented milk were detected in HMfm rats. Consumption of cheese and fermented milk led to similar changes in bacterial metabolism: a decrease in azoreductase activity and NH3concentration and an increase in mucolytic activities. However, specific changes were observed: in HMCp rats, the proportion of ursodeoxycholic resulting from chenodeoxycholic epimerisation was higher; in HMfm rats, α and β-galactosidases were higher than in other groups and both azoreductases and nitrate reductases were lower. The results show that, as for fermented milk, Camembert consumption did not greatly modify the microbiota profile or its major metabolic activities. Ingested micro-organisms were able to survive in part during intestinal transit. These dairy products exert a potentially beneficial influence on intestinal metabolism.

In Vivo Plasma and Urine Folate Binding after Ingestion of3H-Folic Acid and14C-Methyl-Folate

1976 ◽  
Vol 33 (3) ◽  
pp. 415-424 ◽  
Author(s):  
F. P. Retief ◽  
A. du P. Heyns ◽  
Mariëtha Oosthuizen ◽  
O. R. Reenen
Keyword(s):  
Folic Acid

scholarly journals Evaluation of a Novel Therapeutic Approach to Treating Severe Pneumococcal Infection Using a Mouse Model

2009 ◽  
Vol 16 (6) ◽  
pp. 806-810 ◽  
Author(s):  
Nikkol Melnick ◽  
Gowrisankar Rajam ◽  
George M. Carlone ◽  
Jacquelyn S. Sampson ◽  
Edwin W. Ades
Keyword(s):  
Single Dose ◽  
Combination Therapy ◽  
Polymorphonuclear Leukocytes ◽  
Low Dose ◽  
Control Level ◽  
Pneumococcal Infection ◽  
Amino Acid Peptide ◽  
Opsonophagocytic Killing

ABSTRACT P4, a 28-amino-acid peptide, is a eukaryotic cellular activator that enhances specific in vitro opsonophagocytic killing of multiple bacterial pathogens. In a previous study, we successfully recreated this phenomenon in mice in vivo by using a two-dose regimen of P4 and pathogen-specific antibodies, which significantly reduced moribundity in mice. For the present study, we hypothesized that the inclusion of a low-dose antibiotic would make it possible to treat the infected mice with a single dose containing a mixture of P4 and a pathogen-specific antibody. A single dose consisting of P4, intravenous immunoglobulin (IVIG), and ceftriaxone effectively reduced moribundity compared to that of untreated controls (n = 10) by 75% (P < 0.05) and rescued all (10 of 10) infected animals (P < 0.05). If rescued animals were reinfected with Streptococcus pneumoniae and treated with a single dose containing P4, IVIG, and ceftriaxone, they could be rerescued. This observation of the repeated successful use of P4 combination therapy demonstrates a low risk of tolerance development. Additionally, we examined the polymorphonuclear leukocytes (PMN) derived from infected mice and observed that P4 enhanced in vitro opsonophagocytic killing (by >80% over the control level; P < 0.05). This finding supports our hypothesis that PMN are activated by P4 during opsonophagocytosis and the recovery of mice from pneumococcal infection. P4 peptide-based combination therapy may offer an alternative and rapid immunotherapy to treat fulminant pneumococcal infection.

Update on the Treatment of Bacterial Urinary Tract Infections

1981 ◽  
Vol 15 (10) ◽  
pp. 738-750 ◽  
Author(s):  
Neil Massoud
Keyword(s):  
Biological Activity ◽  
Single Dose ◽  
Urinary Tract ◽  
Patient Compliance ◽  
Urinary Tract Infections ◽  
Antimicrobial Agents ◽  
Complex Problem ◽  
Tract Infections

The treatment of urinary tract infections (UTIs) has become a complex problem for the clinical practitioner. An understanding of the pharmacology, pharmacokinetics, and in vivo biological activity of antimicrobial agents is needed, as is an understanding of the variables that may influence patient compliance with medication regimens. Although UTIs are usually treated for 10 to 14 days, shorter treatment schedules of seven to ten days or even single-dose regimens are possible. Guidelines for the treatment of UTIs are presented along with suggestions for increased patient compliance.

scholarly journals Physiologically based kinetic modelling based prediction of in vivo rat and human acetylcholinesterase (AChE) inhibition upon exposure to diazinon

2021 ◽  
Author(s):  
Shensheng Zhao ◽  
Sebastiaan Wesseling ◽  
Bert Spenkelink ◽  
Ivonne M. C. M. Rietjens
Keyword(s):  
Dose Response ◽  
Kinetic Modelling ◽  
Ache Inhibition ◽  
Response Curves ◽  
Alternative Testing ◽  
Dose Response Curves ◽  
Physiologically Based Kinetic Modelling ◽  
Point Of Departure

AbstractThe present study predicts in vivo human and rat red blood cell (RBC) acetylcholinesterase (AChE) inhibition upon diazinon (DZN) exposure using physiological based kinetic (PBK) modelling-facilitated reverse dosimetry. Due to the fact that both DZN and its oxon metabolite diazoxon (DZO) can inhibit AChE, a toxic equivalency factor (TEF) was included in the PBK model to combine the effect of DZN and DZO when predicting in vivo AChE inhibition. The PBK models were defined based on kinetic constants derived from in vitro incubations with liver fractions or plasma of rat and human, and were used to translate in vitro concentration–response curves for AChE inhibition obtained in the current study to predicted in vivo dose–response curves. The predicted dose–response curves for rat matched available in vivo data on AChE inhibition, and the benchmark dose lower confidence limits for 10% inhibition (BMDL10 values) were in line with the reported BMDL10 values. Humans were predicted to be 6-fold more sensitive than rats in terms of AChE inhibition, mainly because of inter-species differences in toxicokinetics. It is concluded that the TEF-coded DZN PBK model combined with quantitative in vitro to in vivo extrapolation (QIVIVE) provides an adequate approach to predict RBC AChE inhibition upon acute oral DZN exposure, and can provide an alternative testing strategy for derivation of a point of departure (POD) in risk assessment.

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