α1-Antitrypsin and Reactive Systemic Amyloidosis

1983 ◽  
Vol 64 (4) ◽  
pp. 453-454 ◽  
Author(s):  
C. P. J. Maury ◽  
A.M. Teppo ◽  
B. Fröseth ◽  
O. Wegelius
Keyword(s):  
Rheumatoid Arthritis ◽  
Biological Activity ◽  
Protease Inhibitor ◽  
Inhibitory Activity ◽  
Systemic Amyloidosis ◽  
Amyloid A ◽  
Control Subjects ◽  
Patient Groups ◽  
The Difference

1. Serum contains amyloid A-degrading activity. This activity is markedly reduced in patients with rheumatoid arthritis (RA) complicated by amyloidosis. α1-Antitrypsin inhibits the degradative activity. To test the hypothesis that the activity of this enzyme is regulated by α1-antitrypsin, we determined the concentrations, elastase-inhibitory activity and phenotypes of α1-antitrypsin in 24 RA patients with and in 26 RA patients without amyloidosis. 2. α1-Antitrypsin concentrations and biological activity were significantly increased in both patient groups compared with control subjects, but there was no difference between the two patient groups. 3. All patients who had developed amyloidosis were of the normal protease inhibitor (Pi) MM-phenotype. 4. We conclude that the difference in the amyloid A-degrading activity between RA patients with or without amyloidosis cannot be accounted for by differences in concentration, activity or Pi type of α1-antitrypsin.

scholarly journals Discrepancy Between SAA and CRP levels Linked to the Difference of SAA/CRP ratio in Early Rheumatoid Arthritis

2021 ◽  
Author(s):  
Hiroshi Uda ◽  
Rika Ebisu ◽  
Keiji Maeda ◽  
Osamu Saiki
Keyword(s):  
Rheumatoid Arthritis ◽  
Early Rheumatoid Arthritis ◽  
Serum Amyloid A ◽  
High Ratio ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Amyloid A ◽  
Follow Up Study ◽  
The Difference

Abstract Objectives Indeed, serum amyloid A (SAA) and C-reactive protein (CRP) reportedly seem to have moderate correlation, but discrepancies between CRP and SAA levels have often been reported in patients with early rheumatoid arthritis (ERA). This study aimed to determine the reasons for this discrepancy. Methods ERA patients (n = 206) were enrolled and treated with anti-RA drugs. Clinical features and disease activities were estimated. CRP and SAA levels were monitored, and the SAA/CRP ratio was compared. Correlations between CRP and SAA levels in individuals and between individuals, and disease activity scores were examined. Results In a follow-up study, the SAA/CRP ratio remained almost constant over time in the same patients. However, SAA/CRP ratios differed widely between patients (0.233–106.3). In patients with high SAA/CRP ratio (>6.52), many (26.2%) had abnormal SAA values only. In patients with low SAA/CRP ratio (<6.52), not a few (6.8%) exhibited abnormal CRP values only. Conclusions The SAA/CRP ratio remained virtually constant in the same patients but differed dramatically between patients, which clarifies the discrepancy between CRP and SAA levels. CRP is the better marker in low-ratio patients, but not in high-ratio patients; the SAA/CRP ratio is critical for its interpretation.

Strategies for Oral Delivery of Metal-Saturated Lactoferrin

2019 ◽  
Vol 20 (11) ◽  
pp. 1046-1051 ◽  
Author(s):  
Przemysław Gajda-Morszewski ◽  
Klaudyna Śpiewak-Wojtyła ◽  
Maria Oszajca ◽  
Małgorzata Brindell
Keyword(s):  
Biological Activity ◽  
Oral Delivery ◽  
Therapeutic Potential ◽  
Structure And Function ◽  
The Difference ◽  
And Function ◽  
First Time

Lactoferrin was isolated and purified for the first time over 50-years ago. Since then, extensive studies on the structure and function of this protein have been performed and the research is still being continued. In this mini-review we focus on presenting recent scientific efforts towards the elucidation of the role and therapeutic potential of lactoferrin saturated with iron(III) or manganese(III) ions. The difference in biological activity of metal-saturated lactoferrin vs. the unmetalated one is emphasized. The strategies for oral delivery of lactoferrin, are also reviewed, with particular attention to the metalated protein.

Synthesis and biological activity of selenopsammaplin A and its analogues as antitumor agents with DOT1L inhibitory activity

2021 ◽  
Vol 35 ◽  
pp. 116072 ◽  
Author(s):  
Hae Ju Han ◽  
Woong Sub Byun ◽  
Gyu Ho Lee ◽  
Won Kyung Kim ◽  
Kyungkuk Jang ◽  
...  
Keyword(s):  
Biological Activity ◽  
Inhibitory Activity ◽  
Antitumor Agents

High disease activity is associated with higher blood pressure in recent onset rheumatoid arthritis patients, post-hoc analyses of IMPROVED study

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
M Gegenava ◽  
SA Bergstra ◽  
H Maassen ◽  
CF Allaart
Keyword(s):  
Rheumatoid Arthritis ◽  
Blood Pressure ◽  
Disease Activity ◽  
Classification Criteria ◽  
Recent Onset ◽  
American College Of Rheumatology ◽  
Cardiovascular Morbidity And Mortality ◽  
The Difference ◽  
Post Hoc ◽  
Acpa Status

Abstract Funding Acknowledgements Type of funding sources: None. Background Rheumatoid arthritis (RA) is a chronic autoimmune disease with a high prevalence of cardiovascular morbidity and mortality. Purpose: purpose of our project was to investigate the association between disease activity and systolic and diastolic blood pressure (SBP, DBP) in patients with recent-onset rheumatoid arthritis (RA 2010 criteria) or undifferentiated arthritis (UA) who were treated to target disease activity score (DAS)<1.6 in the IMPROVED study. Methods: The associations between disease activity and SBP/DBP were tested for 610 patients (364 RA, 246 UA), cross-sectionally and over time. GEE analyses were performed with both SBP and DBP as outcome measures and disease activity categories (DAS<1.6;>1.6 but ≤2.4; >2.4), CRP level, treatment arms or the number of visits on a certain drug as potential predictors in separate analyses. Separate analyses tested potential contributions of gender, anti-cyclic citrullinated peptide antibodies (ACPA) status, and fulfilling the 2010 ACR/EULAR (American college of rheumatology/ European league against rheumatism) classification criteria. In addition association of BP with various levels of disease activity was tested with T-test. Results: At the baseline mean (SD) SBP was 133 (20) and DBP mean (SD) was 80 (10).  SBP > 140mm Hg was observed in 40% of patients and DBP > 90 mm Hg  in 21% of patients. SBP and DBP statistically significantly decreased during 5 years follow up (mainly during year 1), but the difference in mm Hg was small. Estimates from GEE analysis showed that patients with high DAS >2.4 (HDAS) had a statistically significantly higher SBP (average 3 mm Hg higher, 95% CI 1.7; 4.2, p < 0.01), than the patients in with DAS ≤2.4. ANOVA analyses showed a statistically significant association between SBP and DAS. In addition, post hoc analyses showed that patients with HDAS had a statistically significantly higher  SBP (mean (SD) 132 (19) than the patients with DAS < 1.6 (remission) (mean (SD) 129 (20), p < 0.01), and patients in LDAS but DAS≥1.6 had a statistically significantly higher SBP (mean (SD) 131 (19) than the patients in remission (mean (SD)  129 (20), p = 0.02) (Figure 1), whereas no association was found between DAS category and DBP. Gender, ACPA status or fulfilling the 2010 classification criteria did not influence the relation between DAS and blood pressure. Conclusions: In patients with RA or UA, a higher DAS is associated with higher blood pressure, but the clinical impact is unclear. Abstract Figure 1

scholarly journals The Physical Adsorption of Gelatinized Starch with Tannic Acid Decreases the Inhibitory Activity of the Polyphenol against α-Amylase

Foods ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1233
Author(s):  
Yueyi Wang ◽  
Shuangshuang Li ◽  
Fangting Bai ◽  
Junwei Cao ◽  
Lijun Sun
Keyword(s):  
Enzyme Inhibition ◽  
Tannic Acid ◽  
Inhibitory Activity ◽  
Adsorption Property ◽  
Physical Adsorption ◽  
Enzyme Active Site ◽  
Opposite Trend ◽  
Gelatinized Starch ◽  
The Difference

The effects of mixing orders of tannic acid (TA), starch, and α-amylase on the enzyme inhibition of TA were studied, including mixing TA with α-amylase before starch addition (order 1), mixing TA with pre-gelatinized starch before α-amylase addition (order 2) and co-gelatinizing TA with starch before α-amylase addition (order 3). It was found that the enzyme inhibition was always highest for order 1 because TA could bind with the enzyme active site thoroughly before digestion occurred. Both order 2 and 3 reduced α-amylase inhibition through decreasing binding of TA with the enzyme, which resulted from the non-covalent physical adsorption of TA with gelatinized starch. Interestingly, at low TA concentration, α-amylase inhibition for order 2 was higher than order 3, while at high TA concentration, the inhibition was shown with the opposite trend, which arose from the difference in the adsorption property between the pre-gelatinized and co-gelatinized starch at the corresponding TA concentrations. Moreover, both the crystalline structures and apparent morphology of starch were not significantly altered by TA addition for order 2 and 3. Conclusively, although a polyphenol has an acceptable inhibitory activity in vitro, the actual effect may not reach the expected one when taking processing procedures into account.

scholarly journals Sexual Dimorphisms of Adrenal Steroids, Sex Hormones, and Immunological Biomarkers and Possible Risk Factors for Developing Rheumatoid Arthritis

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Alfonse T. Masi ◽  
Azeem A. Rehman ◽  
Laura C. Jorgenson ◽  
Jennifer M. Smith ◽  
Jean C. Aldag
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factors ◽  
Sexual Dimorphism ◽  
Sex Hormones ◽  
Inflammatory Diseases ◽  
Interleukin 2 ◽  
Tumor Necrosis Factor Receptor ◽  
Serum Levels ◽  
Amyloid A ◽  
Neuroendocrine Factors

Innate immunity and immunological biomarkers are believed to be interrelated with sex hormones and other neuroendocrine factors. Sexual dimorphism mechanisms may be operating in certain rheumatic and inflammatory diseases which occur more frequently in women than men, as rheumatoid arthritis (RA). Less data have been available on altered interrelations of the combined neuroendocrine and immune (NEI) systems as risk factors for development of certain diseases. In this study, serological interrelations of NEI biomarkers are analyzed before symptomatic onset of RA (pre-RA) versus control (CN) subjects, stratified by sex. Sexual dimorphism was found in serum levels of acute serum amyloid A (ASAA), soluble interleukin-2 receptor alpha (sIL-2Rα), and soluble tumor necrosis factor receptor 1 (sTNF-R1). Multiple steroidal and hormonal (neuroendocrine) factors also showed highly(p<0.001)significant sexual dimorphism in their assayed values, but less for cortisol(p=0.012), and not for 17-hydroxyprogesterone(p=0.176). After stratification by sex and risk of developing RA, differential NEI correlational patterns were observed in the interplay of the NEI systems between the pre-RA and CN groups, which deserve further investigation.

Taurine Improves the Absorption of a Fat Meal in Patients With Cystic Fibrosis

PEDIATRICS ◽  
1987 ◽  
Vol 80 (4) ◽  
pp. 517-523
Author(s):  
Dominique C. Belli ◽  
Emile Levy ◽  
Pauline Darling ◽  
Claudie Leroy ◽  
Guy Lepage ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Fatty Acid ◽  
Area Under The Curve ◽  
Enzyme Therapy ◽  
Taurine Supplementation ◽  
Control Subjects ◽  
Total Fatty Acids ◽  
The Difference ◽  
Fatty Acid Deficiency ◽  
Fat Meal

The effect of taurine supplementation on the absorption of a fat meal was evaluated in patients with cystic fibrosis. In a cross-over design study, five patients with cystic fibrosis (12.1 ± 2.6 years of age) and three control subjects received either placebo or taurine (30 mg/kg/d) for two 1-week periods, a month apart, followed by a fat meal test. Blood samples were drawn 0, 1, 2, 3, 5, 8 hours after the meal. Four patients with cystic fibrosis and severe steatorrhea despite appropriate enzyme therapy showed a significant (P &lt; .05) improvement in the absorption of triglycerides, total fatty acids, and linoleic acid while receiving taurine supplements. Three control subjects and one child with cystic fibrosis and mild steatorrhea receiving enzyme therapy did not experience such an effect. The difference in triglyceride absorption, when calculated as the area under the curve, receiving and not receiving taurine was significantly (P &lt; .05) correlated with the degree of steatorrhea. Furthermore, in contrast to control subjects, the fatty acid composition of chylomicrons in these four study patients showed important discrepancies with that of the fat meal and was corrected, in part, by taurine supplementation. These results suggest that taurine supplementation could be a useful adjunct in the management of patients with cystic fibrosis with ongoing fat malabsorption and essential fatty acid deficiency.

Methods to study the structure of misfolded protein states in systemic amyloidosis

2021 ◽  
Vol 49 (2) ◽  
pp. 977-985
Author(s):  
Marcus Fändrich ◽  
Matthias Schmidt
Keyword(s):  
Protein Misfolding ◽  
Amyloid Fibrils ◽  
Ex Vivo ◽  
Systemic Amyloidosis ◽  
Structural Basis ◽  
Amyloid A ◽  
Serum Amyloid A Protein ◽  
Proteolytic Stability

Systemic amyloidosis is defined as a protein misfolding disease in which the amyloid is not necessarily deposited within the same organ that produces the fibril precursor protein. There are different types of systemic amyloidosis, depending on the protein constructing the fibrils. This review will focus on recent advances made in the understanding of the structural basis of three major forms of systemic amyloidosis: systemic AA, AL and ATTR amyloidosis. The three diseases arise from the misfolding of serum amyloid A protein, immunoglobulin light chains or transthyretin. The presented advances in understanding were enabled by recent progress in the methodology available to study amyloid structures and protein misfolding, in particular concerning cryo-electron microscopy (cryo-EM) and nuclear magnetic resonance (NMR) spectroscopy. An important observation made with these techniques is that the structures of previously described in vitro formed amyloid fibrils did not correlate with the structures of amyloid fibrils extracted from diseased tissue, and that in vitro fibrils were typically more protease sensitive. It is thus possible that ex vivo fibrils were selected in vivo by their proteolytic stability.

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