Experimental production of elevated serum folate in dogs with intestinal blind loops. II. Nature of bacterially produced folate coenzymes in blind loop fluid

1975 ◽  
Vol 28 (8) ◽  
pp. 925-929 ◽  
Author(s):  
L H Bernstein ◽  
S Gutstein ◽  
G Efron ◽  
G Wager

1972 ◽  
Vol 63 (5) ◽  
pp. 815-819 ◽  
Author(s):  
Leslie H. Bernstein ◽  
Sidney Gutstein ◽  
Gershon Efron ◽  
Gael Wager


The Lancet ◽  
1966 ◽  
Vol 288 (7458) ◽  
pp. 341-342
Author(s):  
ErikM. Magnus


Blood ◽  
1975 ◽  
Vol 46 (4) ◽  
pp. 599-609 ◽  
Author(s):  
ER Eichner ◽  
CJ Paine ◽  
VL Dickson ◽  
MD Jr Hargrove

Abstract We studied the effect of serum folate-binding protein (FBP) on folate radioassays and the relationship of the serum level of unsaturated FBP to the serum folate level in various clinical states. Our modification of a heat-extracted radioassay was compared to a whole serum radioassay. Our results confirmed the existence of elevated serum levels of unsaturated FBP in some normal subjects, in some women taking oral contraceptives, and in most patients with uremia. Elevated levels of unsaturated FBP will produce falsely low results in folate radioassay unless the FBP has been destroyed by heat, as was done in the modified radioassay here presented. In normal and uremic subjects, serum folate and unsaturated FBP levels tended to correlate, whereas in patients taking large doses of folic acid the level of unsaturated FBP fell as the level of serum folate rose.



2019 ◽  
Vol 67 (8) ◽  
pp. 1110-1117 ◽  
Author(s):  
Clóvis Paniz ◽  
Maylla Rodrigues Lucena ◽  
Juliano Felix Bertinato ◽  
Felipe Rebello Lourenço ◽  
Bruna Cipriano A Barros ◽  
...  

Patients with hereditary spherocytosis (HS) have increased rates of erythropoiesis and higher folate requirements. In a case-control study of patients with HS, we evaluated the associations between the use of 5 mg folic acid (FA) daily and serum concentrations of folate, unmetabolized folic acid (UMFA), interleukin (IL)-6, IL-8, IL-10, interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α); and mRNA expression of dihydrofolate reductase (DHFR), methylene tetrahydrofolate reductase (MTHFR), IL8, IFNG and TNFA genes. Total serum folate and folate forms were measured in 27 patients with HS (21 users [HS-U] and 6 non-users [HS-NU] of supplemental FA) and 54 healthy controls not consuming 5 mg/day supplemental FA. Each patient was matched to two controls based on age, sex and body mass index. The mononuclear leucocyte mRNA expression of relevant genes and their products were determined. Serum folate, UMFA, 5-methyl-tetrahydrofolate (5-methyl-THF) and tetrahydrofolate (THF) concentrations were significantly higher in HS-U compared with matched healthy controls (p<0.001, n=42). HS-NU had lower serum folate concentrations than matched healthy controls (p=0.044, n=12). HS-U and HS-NU presented similar hematological and biochemical markers profiles. No differences were found between HS-U and HS-NU for cytokine serum concentrations and mRNA expression genes. DHFR mRNA expression was higher in HS-U than in HS-NU. The use of high daily doses of FA for treatment of patients with HS may be excessive and is associated with elevated serum UMFA and elevated DHFR mRNA expression. It is not known whether long-term high-dose FA use by patients with HS might have adverse health effects.



The Lancet ◽  
1966 ◽  
Vol 287 (7451) ◽  
pp. 1339-1342 ◽  
Author(s):  
A.V. Hoffbrand ◽  
Soad Tabaqchali ◽  
D.L. Mollin


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1300-1300
Author(s):  
Sally P. Stabler ◽  
Robert H. Allen ◽  
Mary Ann Johnson ◽  
Dorothy B. Hausman ◽  
Adam Davey ◽  
...  

Abstract Anemia in seniors is associated with increased mortality and frailty. It is important to determine the cause of anemia in order to initiate specific therapies. We studied cobalamin (Cbl) and folate status with other clinical and laboratory parameters associated with anemia in 234 centenarians from north Georgia aged 98–108 years, 197 female, 46 African-American. The Cbl and folate dependant metabolites included methylmalonic acid (MMA), total homocysteine (Hcys) and 2-methylcitric acid (MC). MMA, MC and Hcys are elevated in clinical Cbl deficiency. MC is also elevated with even mild renal insufficiency. Metabolites were assayed by capillary gas chromatography/mass spectrometry. The median hemoglobin (Hgb) and hematocrit (Hct) were 12.0 g/dL and 35.2 %. Severe anemia (Hgb &lt; 8 g/dL) occurred in only 1 white female with serum ferritin of 10 ng/mL. The 10th percentile for hemoglobin was 10.0 g/dL, and in this group, serum MC was increased (p = 0.021), albumin trended lower (p = 0.056) but serum folate, Cbl, Hcys, MMA, and creatinine were not significantly different. Univariate analysis between variables for the whole cohort showed that Hgb was inversely correlated with Hcys (p = 0.028), MC (p = 0.003), creatinine (p = 0.030) and directly with albumin (p = 0.001). In multivariate analysis, albumin was the strongest positive predictor of Hgb and MC was significantly inversely related, whereas creatinine and Hcys were no longer independent determinants. Elevated MMA with low Cbl was common in this cohort but not associated with anemia. Even those above the 90th percentile for MMA (844–8080 nmol/L) actually had higher Hgb as compared to the rest of the cohort, 12.3 vs. 12.0 mg/dL (p = 0.096). Folate status was high in this cohort (50th percentile (12.9 ng/mL) and those taking a multivitamin (33%) had 1.5 fold higher serum folate (p &lt; 0.001), 17 % lower Hcy (p = 0.001) and 24 % lower MMA (p = 0.045) but no difference in Hgb. The only racial difference was that MMA was lower in African-Americans (p &lt;0.001) and the only sex difference was that creatinine was higher in males (p = 0.025). Those with MC above the 90th percentile (&gt; 415 nmol/L) had lower Hgb (p = 0.038), higher creatinine (p = 0.003), Hcy (p = 0.003) and MMA (p = 0.060). Ferritin was less than 50 ng/mL in 10/22 subjects with the lowest 10th percentile Hgb value (&lt; 10.0 g/dL). One subject had apparent folate deficiency and 7/22 had serum creatinine &gt; 1.3 mg/dL. Two subjects with MCV &gt; 100 fl had renal insufficiency. In conclusion, 1. High serum 2-methylcitric acid and low serum albumin predict anemia in centenarians. 2. Serum 2-methylcitric acid may be a sensitive indicator of renal failure- associated anemia. 3. Cbl deficiency was not associated with anemia in this cohort with high folate status.



Author(s):  
Wolfgang Herrmann ◽  
Sonia Isber ◽  
Rima Obeid ◽  
Markus Herrmann ◽  
Muhidien Jouma

AbstractBackground: Hyperhomocysteinemia, a proxy measure for the nutritional status of the B vitamins, may be involved in the etiology of preeclampsia via inducing endothelial dysfunction. Asymmetric dimethylarginine (ADMA) is an inhibitor of NO-synthase that may adversely affect the endothelium.Materials and methods: We investigated serum concentrations of folate, vitamin BResults: Higher concentrations of Hcy, cystathionine and methylmalonic acid (MMA) were closely linked to a lower status of the B vitamins. Higher concentrations of Hcy and cystathionine were observed in the preeclamptic group than in the matched controls (median Hcy 9.3 vs. 6.0μmol/L; median cystathionine 284 vs. 232nmol/L). Serum folate was significantly lower in patients than in controls (16.4 vs. 36.0nmol/L). Folate supplementation was less likely to be used in preeclamptic women. Concentrations of MMA were elevated in patients and controls and did not differ significantly between the two groups. Median plasma concentrations of ADMA were significantly lower in asymptomatic women than in those who developed preeclampsia before the 37th week of gestation (0.61 vs. 0.68μmol/L).Conclusions: Elevated serum concentrations of Hcy, cystathionine and MMA indicate poor status of the B vitamins during pregnancy. The adverse effect of Hcy on endothelial function might be related to ADMA in early-onset preeclampsia. More emphasis should be placed on increasing the intake of B vitamins in pregnant women from developing countries.



Blood ◽  
1949 ◽  
Vol 4 (7) ◽  
pp. 803-815 ◽  
Author(s):  
D. G. CAMERON ◽  
G. M. WATSON ◽  
L. J. WITTS

Abstract 1. The literature concerning attempts to produce macrocytic anemia of the liver-deficiency type in animals by operations on the gastrointestinal tract has been reviewed. Operations on the stomach have failed consistently to produce such an anemia, but success has been achieved by operations on the small intestine with the creation of blind loops or intestinal stenosis. 2. The technic we have used to produce macrocytic anemia in the rat is described in detail. The essentials are that the blind loop should fill with peristalsis and that it should not be too low down in the small intestine. 3. Anemia does not usually develop until an interval of several weeks or months after the operation. It is then macrocytic in type and acute in course. 4. The anemia is probably dependent on stagnation in the blind loop and a change in the bacterial flora of the small intestine.



Author(s):  
Shuai Yuan ◽  
Paul Carter ◽  
Mathew Vithayathil ◽  
Siddhartha Kar ◽  
Amy M. Mason ◽  
...  

Abstract Background Folate, vitamin B6 and vitamin B12 have been associated with digestive system cancers. We conducted a two-sample Mendelian randomisation study to assess the causality of these associations. Methods Two, one and 14 independent single nucleotide polymorphisms associated with serum folate, vitamin B6 and vitamin B12 at the genome-wide significance threshold were selected as genetic instruments. Summary-level data for the associations of the vitamin-associated genetic variants with cancer were obtained from the UK Biobank study including 367,561 individuals and FinnGen consortium comprising up to 176,899 participants. Results Genetically predicted folate and vitamin B6 concentrations were not associated with overall cancer, overall digestive system cancer or oesophageal, gastric, colorectal or pancreatic cancer. Genetically predicted vitamin B12 concentrations were positively associated with overall digestive system cancer (ORSD, 1.12; 95% CI 1.04, 1.21, p = 0.003) and colorectal cancer (ORSD 1.16; 95% CI 1.06, 1.26, p = 0.001) in UK Biobank. Results for colorectal cancer were consistent in FinnGen and the combined ORSD was 1.16 (95% CI 1.08, 1.25, p < 0.001). There was no association of genetically predicted vitamin B12 with any other site-specific digestive system cancers or overall cancer. Conclusions These results provide evidence to suggest that elevated serum vitamin B12 concentrations are associated with colorectal cancer.



Blood ◽  
1975 ◽  
Vol 46 (4) ◽  
pp. 599-609
Author(s):  
ER Eichner ◽  
CJ Paine ◽  
VL Dickson ◽  
MD Jr Hargrove

We studied the effect of serum folate-binding protein (FBP) on folate radioassays and the relationship of the serum level of unsaturated FBP to the serum folate level in various clinical states. Our modification of a heat-extracted radioassay was compared to a whole serum radioassay. Our results confirmed the existence of elevated serum levels of unsaturated FBP in some normal subjects, in some women taking oral contraceptives, and in most patients with uremia. Elevated levels of unsaturated FBP will produce falsely low results in folate radioassay unless the FBP has been destroyed by heat, as was done in the modified radioassay here presented. In normal and uremic subjects, serum folate and unsaturated FBP levels tended to correlate, whereas in patients taking large doses of folic acid the level of unsaturated FBP fell as the level of serum folate rose.



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