Experimental Production of Elevated Serum Folate in Dogs with Intestinal Blind Loops: Relationship of Serum Levels to Location of the Blind Loop

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


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.


Nutrients ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 4004
Author(s):  
Partyka Robert ◽  
Mroczek Alina ◽  
Duda Sylwia ◽  
Malinowska-Borowska Jolanta ◽  
Buczkowska Marta ◽  
...  

Higher serum phosphorus has detrimental health effects. Even high-normal rage sP is associated with worse outcomes. The relationship of serum phosphorus with prognostic markers in heart failure remains unclear. We investigated the association of serum phosphorus with heart failure prognostic factors and risk of mortality related to serum phosphorus. In 1029 stable heart failure patients, we investigated the distribution of markers of more advanced heart failure stage across quintiles of serum phosphorus and estimated the relative risk of mortality in comparison to reference. Higher serum phosphorus levels sP were associated with markers of a worse outcome. The best survival was observed in low-normal serum levels. The unadjusted hazard ratio for mortality increased toward higher phosphorus quintiles but not to lower levels of sP. The correction for age, sex, BMI, percent weight loss, inflammation, kidney function, and LVEF did not modify the risk profile substantially. The adjustment for NYHA, natriuretic peptides, serum sodium, and treatment characteristics broke down the risk relationship completely. A higher serum phosphorus is associated with markers of a more risky profile of heart failure. Elevated serum levels of phosphorus sP does not provide independent prognostic information beyond the strongest markers of the severity of the syndrome. The potential involvement of higher serum phosphorus as a mediator in the pathophysiology of heart failure warrants further study.


Author(s):  
Bianca Mages ◽  
Thomas Fuhs ◽  
Susanne Aleithe ◽  
Alexandra Blietz ◽  
Constance Hobusch ◽  
...  

AbstractIn the setting of ischemic stroke, the neurofilament subunit NF-L and the microtubule-associated protein MAP2 have proven to be exceptionally ischemia-sensitive elements of the neuronal cytoskeleton. Since alterations of the cytoskeleton have been linked to the transition from reversible to irreversible tissue damage, the present study investigates underlying time- and region-specific alterations of NF-L and MAP2 in different animal models of focal cerebral ischemia. Although NF-L is increasingly established as a clinical stroke biomarker, MAP2 serum measurements after stroke are still lacking. Therefore, the present study further compares serum levels of MAP2 with NF-L in stroke patients. In the applied animal models, MAP2-related immunofluorescence intensities were decreased in ischemic areas, whereas the abundance of NF-L degradation products accounted for an increase of NF-L-related immunofluorescence intensity. Accordingly, Western blot analyses of ischemic areas revealed decreased protein levels of both MAP2 and NF-L. The cytoskeletal alterations are further reflected at an ultrastructural level as indicated by a significant reduction of detectable neurofilaments in cortical axons of ischemia-affected areas. Moreover, atomic force microscopy measurements confirmed altered mechanical properties as indicated by a decreased elastic strength in ischemia-affected tissue. In addition to the results from the animal models, stroke patients exhibited significantly elevated serum levels of MAP2, which increased with infarct size, whereas serum levels of NF-L did not differ significantly. Thus, MAP2 appears to be a more sensitive stroke biomarker than NF-L, especially for early neuronal damage. This perspective is strengthened by the results from the animal models, showing MAP2-related alterations at earlier time points compared to NF-L. The profound ischemia-induced alterations further qualify both cytoskeletal elements as promising targets for neuroprotective therapies.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Danielle Perez-Bercoff ◽  
Hélène Laude ◽  
Morgane Lemaire ◽  
Oliver Hunewald ◽  
Valérie Thiers ◽  
...  

AbstractAPOBEC3 (A3) enzymes are best known for their role as antiviral restriction factors and as mutagens in cancer. Although four of them, A3A, A3B, A3F and A3G, are induced by type-1-interferon (IFN-I), their role in inflammatory conditions is unknown. We thus investigated the expression of A3, and particularly A3A and A3B because of their ability to edit cellular DNA, in Systemic Lupus Erythematosus (SLE), a chronic inflammatory disease characterized by high IFN-α serum levels. In a cohort of 57 SLE patients, A3A and A3B, but also A3C and A3G, were upregulated ~ 10 to 15-fold (> 1000-fold for A3B) compared to healthy controls, particularly in patients with flares and elevated serum IFN-α levels. Hydroxychloroquine, corticosteroids and immunosuppressive treatment did not reverse A3 levels. The A3AΔ3B polymorphism, which potentiates A3A, was detected in 14.9% of patients and in 10% of controls, and was associated with higher A3A mRNA expression. A3A and A3B mRNA levels, but not A3C or A3G, were correlated positively with dsDNA breaks and negatively with lymphopenia. Exposure of SLE PBMCs to IFN-α in culture induced massive and sustained A3A levels by 4 h and led to massive cell death. Furthermore, the rs2853669 A > G polymorphism in the telomerase reverse transcriptase (TERT) promoter, which disrupts an Ets-TCF-binding site and influences certain cancers, was highly prevalent in SLE patients, possibly contributing to lymphopenia. Taken together, these findings suggest that high baseline A3A and A3B levels may contribute to cell frailty, lymphopenia and to the generation of neoantigens in SLE patients. Targeting A3 expression could be a strategy to reverse cell death and the generation of neoantigens.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nurshad Ali ◽  
Abu Hasan Sumon ◽  
Khandaker Atkia Fariha ◽  
Md Asaduzzaman ◽  
Rahanuma Raihanu Kathak ◽  
...  

AbstractObesity is a global health concern because of its increasing trend both in developed and developing countries. A limited number of studies have evaluated the association of liver enzymes with both general and abdominal obesity in the general population; data for the Bangladeshi population are not available yet. This study aimed to assess the relationship of serum liver enzymes activity with both general and abdominal obesity in Bangladeshi adults. In total, 540 blood samples were obtained from the participants (388 males and 152 females) and analyzed for serum levels of ALT, AST, GGT, and ALP using standard methods. General obesity was defined as body mass index (BMI) ≥ 27.5 kg/m2 and abdominal obesity was defined as waist circumference (WC) ≥ 90 cm in males and ≥ 80 cm in females. The relationship between liver enzymes and obesity was evaluated by multivariate logistic regression models. Overall, 58% of participants in the general obesity group and 55% of the participants in the abdominal obesity group had at least one or more elevated levels of liver enzymes. The prevalence of elevated liver enzymes was significantly higher in the obesity group compared to the normal BMI and WC groups (p < 0.05 for all cases). The mean level of serum ALT, AST and GGT were significantly higher in the obesity group than the normal BMI group (p < 0.05). In the WC groups, mean AST and GGT were significantly higher in the obesity group compared to the normal group (p < 0.05). In regression analysis, serum levels of ALT showed an independent and significant association with general obesity, whereas, serum GGT showed a significant association with both general and abdominal obesity. In conclusion, a high prevalence of elevated liver enzymes was observed among participants included in the present study. Of the four enzymes, serum GGT was independently associated with both general and abdominal obesity. Further studies are required to understand the complex relationship between liver enzymes and obesity in the general population.


Endocrinology ◽  
2016 ◽  
Vol 158 (2) ◽  
pp. 419-430 ◽  
Author(s):  
Zhaofei Wu ◽  
M. Elena Martinez ◽  
Donald L. St. Germain ◽  
Arturo Hernandez

Abstract The role of thyroid hormones (THs) in the central regulation of energy balance is increasingly appreciated. Mice lacking the type 3 deiodinase (DIO3), which inactivates TH, have decreased circulating TH levels relative to control mice as a result of defects in the hypothalamic-pituitary-thyroid axis. However, we have shown that the TH status of the adult Dio3−/− brain is opposite that of the serum, exhibiting enhanced levels of TH action. Because the brain, particularly the hypothalamus, harbors important circuitries that regulate metabolism, we aimed to examine the energy balance phenotype of Dio3−/− mice and determine whether it is associated with hypothalamic abnormalities. Here we show that Dio3−/− mice of both sexes exhibit decreased adiposity, reduced brown and white adipocyte size, and enhanced fat loss in response to triiodothyronine (T3) treatment. They also exhibit increased TH action in the hypothalamus, with abnormal expression and T3 sensitivity of genes integral to the leptin-melanocortin system, including Agrp, Npy, Pomc, and Mc4r. The normal to elevated serum levels of leptin, and elevated and repressed expression of Agrp and Pomc, respectively, suggest a profile of leptin resistance. Interestingly, Dio3−/− mice also display elevated locomotor activity and increased energy expenditure. This occurs in association with expanded nighttime activity periods, suggesting a disrupted circadian rhythm. We conclude that DIO3-mediated regulation of TH action in the central nervous system influences multiple critical determinants of energy balance. Those influences may partially compensate each other, with the result likely contributing to the decreased adiposity observed in Dio3−/− mice.


2000 ◽  
Vol 74 (5) ◽  
pp. 2443-2446 ◽  
Author(s):  
Jingwu Xu ◽  
Ali Ahmad ◽  
James F. Jones ◽  
Riccardo Dolcetti ◽  
Emanuela Vaccher ◽  
...  

ABSTRACT Transforming growth factor β (TGF-β) is an immunosuppressive cytokine which can induce immunoglobulin A (IgA) switch and Epstein-Barr virus (EBV) replication in latently infected cells. Here we report elevated serum levels of TGF-β in various EBV-associated diseases correlating positively with EBV-specific IgA titers and negatively with IgM titers, suggesting a role for this cytokine in the pathogenesis of these diseases.


2016 ◽  
Vol 44 (06) ◽  
pp. 1111-1125 ◽  
Author(s):  
Muhammad Jahangir Hossen ◽  
Mi-Yeon Kim ◽  
Jae Youl Cho

Xanthium strumarium L. (Asteraceae), a traditional Chinese medicine, is prescribed to treat arthritis, bronchitis, and rhinitis. Although the plant has been used for many years, the mechanism by which it ameliorates various inflammatory diseases is not yet fully understood. To explore the anti-inflammatory mechanism of methanol extracts of X. strumarium (Xs-ME) and its therapeutic potential, we used lipopolysaccharide (LPS)-stimulated murine macrophage-like RAW264.7 cells and human monocyte-like U937 cells as well as a LPS/D-galactosamine (GalN)-induced acute hepatitis mouse model. To find the target inflammatory pathway, we used holistic immunoblotting analysis, reporter gene assays, and mRNA analysis. Xs-ME significantly suppressed the up-regulation of both the activator protein (AP)-1-mediated luciferase activity and the production of LPS-induced proinflammatory cytokines, including interleukin (IL)-1[Formula: see text], IL-6, and tumor necrosis factor (TNF)-[Formula: see text]. Moreover, Xs-ME strongly inhibited the phosphorylation of mitogen-activated protein kinase (MAPK) in LPS-stimulated RAW264.7 and U937 cells. Additionally, these results highlighted the hepatoprotective and curative effects of Xs-ME in a mouse model of LPS/D-GalN-induced acute liver injury, as assessed by elevated serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and histological damage. Therefore, our results strongly suggest that the ethnopharmacological roles of Xs-ME in hepatitis and other inflammatory diseases might result from its inhibitory activities on the inflammatory signaling of MAPK and AP-1.


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