Search

In this pilot study, we carried out metabolic profiling of patients with rheumatoid arthritis (RA) starting therapy with biological disease-modifying antirheumatic drugs (bDMARDs). The main aim of the study was to assess the occurring metabolic changes associated with therapy success and metabolic pathways involved. In particular, the potential of the metabolomics profiles was evaluated as therapeutically valuable prognostic indicators of the effectiveness of bDMARD treatment to identify responders versus non-responders prior to implementing treatment. Plasma metabolomic profiles of twenty-five patients with RA prior bDMARD treatment and after three months of therapy were obtained by 1 H NMR, liquid chromatography - mass spectrometry, and gas chromatography - mass spectrometry and evaluated by statistical and multivariate analyses. In the group of responders, significant differences in their metabolic patterns were seen after three months of the bDMARD therapy compared with profiles prior to treatment. We identified 24 metabolites that differed significantly between these two-time points mainly belonging to amino acid metabolism, peptides, lipids, cofactors, and vitamins and xenobiotics. Eleven metabolites differentiated responders versus non-responders before treatment. Additionally, N-acetylglucosamine and N-acetylgalactosamine (GlycA) and N-acetylneuraminic acid (GlycB) persisted significant in comparison responders to non-responders after three months of therapy. Moreover, those two metabolites indicated prediction of response potential by results of receiver-operating characteristic (ROC) curve analysis. The applied analysis provides novel insights into the metabolic pathways involved in RA patient's response to bDMARD and therapy effectiveness. GlycA and GlycB are promising biomarkers to identify responding patients prior onset of bDMARD therapy., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Physicochemical methods are the primary tests used to ensure that batches of meningococcal polysaccharide (PS) antigens are manufactured consistently to those shown to be safe and effective in clinical trials. Although modern physicochemical methods of analysis providing structural information about the antigens have been developed and used, simpler assays, which can be readily validated, are still in use for polysaccharide batch release. The simple and cheap method for Neisseria meningitidis serogroup W or Y polysaccharide (MenW or MenY PS) content quantification has been developed. This colorimetric method is based on the galactose or glucose quantification in MenW or MenY PS hydrolysate, respectively. Intra- and inter-assay precision and accuracy of the novel method have been demonstrated, in comparison to the same properties of the current regulatory approved method for the same purpose - sialic acid quantification. We provided the calculation of the possible future regulatory requirement for the galactose or glucose content in MenW or MenY PS, respectively, and revealed in detail the stoichiometric calculation behind it., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objective: The objective of this study is to assess the association of blood and urinary oxidative stress parameters and inflammatory markers in women with gestational hypertension and preeclampsia., Design and Methods: Malondialdehyde, protein bound sialic acid and C-reactive protein were estimated in serum and urine of pregnant women diagnosed with preeclampsia (n=30) and gestational hypertension (n=30) and the results were compared with 30 normal pregnant women., Results: Whole blood glutathione level was reduced, and malondialdehyde and C-reactive protein levels were significantly higher and correlated with each other in preeclampsia (p<0.05). Urinary malondialdehyde significantly correlated with urinary protein bound sialic acid in preeclampsia (r=0.412; p=0.02). Receiver operating curve analysis of serum protein bound sialic acid and serum malondialdehyde showed reasonable cutoff values for the differential diagnosis of preeclampsia., Conclusions: Oxidative stress and inflammatory response are greater in women with preeclampsia in comparison to pregnant women with gestational hypertension and there is an association between oxidative stress and inflammatory response., (Copyright © 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Serum total sialic acid (TSA) concentration is a sensitive marker of excessive alcohol consumption and is the sum of protein-bound sialic acid, lipid-bound sialic acid (LSA), and free sialic acid. The LSA is the fraction of SA attached to gangliosides that are transported in the blood by the lipoproteins. In this article, the effect of chronic alcohol consumption on the serum levels of LSA was evaluated. The objective of the study was to understand the mechanism of elevated serum TSA concentration during alcohol abuse. Additionally, the association of LSA with serum lipid profile was tested. For this purpose, the levels of LSA, TSA, lipids, lipoproteins, and apolipoproteins (apos) in the sera of 106 alcoholics were measured. The serum level of LSA in alcohol abusers was significantly elevated. This increase was because of the elevated level of LSA in patients drinking alcohol up to 2 days before sampling. The elevated level of LSA positively correlated with TSA, and also with biochemical indices of hepatocellular injury such as aspartate aminotransferase and gamma-glutamyltransferase, but did not correlate with any lipids, apos, and lipoproteins. The increase in LSA level is not related with the status of serum lipid profile but is related to the liver status estimated by the biochemical markers of liver cell damage. On the basis of our results, we conclude that the elevated level of LSA in alcohol abusers contributes to an increase in the serum concentration of TSA, and contrary to TSA, is affected by the status of liver cells., (2010 Elsevier Inc. All rights reserved.)

Objectives: To investigate and discuss the total-, lipid-associated, and thrombocyte-sialic acid levels in chronic heart failure (CHF) patients., Design and Methods: Thirty-one chronic heart failure patients and 38 healthy controls were included in the study. Serum total sialic acid (TSA), lipid associated sialic acid (LASA), thrombocyte sialic acid (TrSA) were determined together with the traditional inflammation and prognostic markers., Results: Serum TSA levels were significantly higher in patient group (3.08 + or - 0.33 mmol/L) than control group (2.60 + or - 0.17 mmol/L). Serum LASA, homocysteine, high-sensitivity CRP, brain natriuretic peptide and erythrocyte sedimentation rate were also significantly higher in patient group. TrSA levels were not significant between the groups., Conclusion: TSA and LASA levels increase in CHF, independent from coronary artery disease. TrSA levels were not found to be a prognostic or valuable marker for CHF patients. Acute phase response and lipid associated portions of SA are thought to be responsible for SA rise in CHF., (Copyright 2009 The Canadian Society of Clinical Chemists. All rights reserved.)

Low-grade and chronic inflammation related to excessive body weight can increase the risk for type 2 diabetes and cardiovascular disease, whereas the intake of antioxidant nutrients appears to produce anti-inflammatory effects. The purpose of this observational study was to assess the potential relationships between serum SA levels, metabolic syndrome features, and dietary selenium intake to test the hypothesis that this antioxidant micronutrient may also have anti-inflammatory properties in healthy young adults. Forty-three healthy participants with a mean age of 18.0 +/- 0.93 years and a mean body mass index of 22.2 +/- 2.7 kg/m(2) were enrolled. Anthropometric, body composition, and blood pressure determinations were measured as well as serum lipid profile, glucose, insulin, and SA concentrations. Nutritional intake was estimated by a computerized, validated semiquantitative food frequency questionnaire. The findings included a positive correlation between SA and triacylglycerol levels (r = 0.317, P = .038) and a trend to significance with the homeostatic model assessment of insulin resistance index (r = 0.297, P = .053). Moreover, subjects with higher dietary selenium intake showed statistically lower SA levels compared with subjects with lower dietary selenium intake (1.8 +/- 0.4 vs 2.1 +/- 0.4 mmol/L, P = .037), while dietary selenium negatively correlated with SA (r = -0.331, P = .030) and triacylglycerol levels (r = -0.312, P = .041). It can be concluded that a relationship of SA, an inflammatory marker, with metabolic syndrome features such as lipid profile impairment and insulin resistance has been envisaged. In addition, we report (apparently for the first time) a negative association between SA and selenium intake, a recognized antioxidant trace element, in healthy young subjects, reinforcing the view of selenium as a potential anti-inflammatory nutrient.

Objectives: Early prediction of severe acute pancreatitis is one of the problems in clinical practice. Since many diseases are associated with alteration in glycosylation, in this work we studied sialylation of transferrin and serum proteins in acute pancreatitis., Design and Methods: Sialylation was analyzed during first eight days of hospitalization of 30 patients and compared to 28 healthy controls. Transferrin sialylation was measured using enzyme linked lectin assay, while sialic acid on proteins was measured using resorcinol method., Results: Both analyzed parameters changed during studied period. The change in transferrin sialylation between Day1 and Day2 of hospitalization was shown to be an early prognostic marker of acute pancreatitis, with better sensitivity (88.9%) and specificity (90.5%) than other markers tested., Conclusions: Sialylation of transferrin and total serum proteins reflects the intensity of inflammatory response during acute pancreatitis and could be used as prognostic parameter for disease severity.

Background: Cardiovascular diseases are important factors in mortality and morbidity of dialysis patients. Cardiovascular risk assessment is important in order to arrange the treatment strategies. The aim of the study was to investigate the relationship between carotid atherosclerosis and various CVD risk factors in dialysis patients., Methods: 22 HD and 54 PD patients were included in the study. Carotid artery intima media thickness (IMT) and plaque score (PS) were obtained by B-mode ultrasonography for each participant. Uric acid, albumin, bilirubin, lipid profile, apolipoprotein A-l (apo A-l), apolipoprotein B (apo B), lipoprotein(a) [Lp(a)], high-sensitivity CRP (hs-CRP), homocysteine (Hcy), vitamin A, vitamin E, sialic acid (SA) and thiobarbituric acid-reactive substances (TBARS) were determined. The differences of the cardiovascular risk factors between the patients according to the treatment modality and the comparison of the risk factors as indicators of IMT and PS were investigated., Results: There was no significant difference in IMT and PS between the two groups. SA, TBARS, hs-CRP, total, HDL- and LDL-cholesterol, white blood cell (WBC) and erythrocyte sedimentation rate (ESR) levels were significantly higher; albumin levels were significantly lower in PD group. In multiple regression analysis, only bilirubin for IMT and SA for PS were independent predictors., Conclusions: SA can be a superior marker to hs-CRP in PD patients; however, hs-CRP seems to be a more valuable marker than SA in HD patients according to the correlation analysis. This study provides information and opportunity for comparison of relatively new cardiovascular risk markers in hemodialysis and peritoneal dialysis patients using carotid atherosclerosis as an objective assessment criterion.

The global burden posed by cardiovascular disease (CVD), due to a rising incidence of known risk factors, underlines an urgent need to identify other potential risk factors. Sialic acid (SA), an abundant terminal monosaccharide of glycoconjugates, is a possible risk factor for CVD. Although large-scale epidemiological surveys have shown that serum total sialic acid (TSA) is positively associated with mortality from coronary artery disease (CAD) and stroke, studies investigating the correlation between serum TSA and the severity of atherosclerosis are conflicting. Clinical and epidemiological studies indicate that serum TSA is a marker of a sustained inflammatory response in CVD, rather than causal in nature. Data also indicates ethnic variation in baseline TSA. This article reviews current methods for determining serum TSA and evidence supporting serum TSA as a risk factor for CVD. Potential mechanisms for this role are examined. The use of serum TSA as a marker of atherosclerotic disease is evaluated.

Although plasma carbohydrate-deficient transferrin (CDT) is considered a viable biochemical marker for chronic alcohol consumption, it is valid only when an individual's daily alcohol consumption exceeds 60 g. In addition, it is less sensitive in women drinkers than in men drinkers. We have established that chronic alcohol consumption impairs the hepatic sialylation of a number of glycoproteins by specifically down-regulating Gal-beta-1,4GlcNAc alpha2,6-sialyltransferase mRNA. Significantly, we found that chronic ethanol consumption markedly inhibits hepatic sialylation of apolipoprotein J (Apo J), a 70-kDa N-glycosylated protein of plasma HDL. Because the sialic-acid index of Apo J (SIJ; moles of sialic acid per mole of Apo J protein) is approximately seven times more than that for transferrin (28 vs. 4), we have evaluated whether plasma SIJ would be an even more sensitive marker for chronic ethanol consumption than CDT in both rats and human subjects. The method involves immunoaffinity purification of plasma HDL-Apo J, followed by its sialic acid determination. We have found that chronic ethanol feeding resulted in loss of sialic acid residues of plasma HDL-Apo J in rats. This loss of sialic acid was positively correlated with both amount and duration of ethanol treatment. In human subjects, an intake of about 60 g of alcohol for 30 days led to almost 50% (P <.01) depletion of sialic acid from plasma HDL-Apo J. Further, we established that there was a positive correlation of alteration in SIJ with alcohol consumption, detoxification, abstinence, and relapse in human alcohol-dependent patients (sensitivity, 90%-92%). In addition, plasma SIJ was decreased by 50%-57% (P <.01) in both male and female alcohol-dependent subjects. We suggest that plasma SIJ can be used as a viable marker for early detection of chronic alcohol consumption in human beings.

Objectives: This study was undertaken to establish the diagnostic utility of serum total sialic acid (TSA) for patients with cholangiocarcinoma (CCA)., Design and Methods: Serum TSA was determined in 89 histologically confirmed CCA patients, 38 with benign hepatobiliary diseases (BHD) and 43 healthy persons. To check whether the test could adequately discriminate between these groups, complete statistical Receiver Operating Characteristic (ROC) curves were analyzed., Results: The mean value of serum TSA in CCA patients (2.75 +/- 0.67 mmol/L) was significantly higher than that in the BHD (2.33 +/- 0.69 mmol/L p < 0.002) and healthy persons (1.89 +/- 0.46 mmol/L p < 0.001) groups. The areas under the ROC curves were 0.6699 and 0.8558, respectively. A cut-off value of 2.33 mmol/L discriminated between the CCA, BHD and healthy groups with a sensitivity of 71.9% and a positive predictive value range of 80 to 89%., Conclusion: Determination of TSA yielded high diagnostic values for differentiating between CCA, BHD and healthy persons. The determination of serum TSA would be most useful as an adjunct diagnosis rather than an early detection and screening tool because of the apparent nonspecificity of SA to a given disease.

In this work we identified in adult and juvenile freshwater prawn, Macrobrachium rosenbergii, three major type of circulating hemocytes: fusiform; rounded; and large ovoid hemocytes. Rounded and large hemocytes represent the first defense line, since this type of cells exerts phagocytic activity as well as lectin synthesis. Considering that glycosylation plays important roles in cell communication and as a target for pathogenic microorganisms, in this report was also described the main glycosidic modifications that occur in the large and rounded hemocytes from the freshwater prawn during maturation as determined with lectins. Neu5Acalpha2,6Gal, was identified homogeneously distributed in the membrane in 90% of hemocytes from juvenile organisms. Maturation of the freshwater prawn induced a decrease or complete loss of Neu5Acalpha2,6Gal residues that were replaced with Neu5Acalpha2,3 molecules in practically all hemocytes from adult organisms. This change was paralleled by a diminution in 9-O-acetyl-neuraminic acid (Neu5,9Ac(2)) expression. T and Tn antigens (Galbetal,3 GalNAcalpha1-0-Ser/Thr or GalNAcalpha1-0-Ser/Thr, respectively), as well as N-glycosidically linked glycans, seem to be highly conserved throughout maturation. Our results show that sialylation of freshwater prawn hemocytes is modulated throughout the maturation process.

Changes in bone modeling and remodeling in the tibia of growing rats within 30 days of ovariectomy (ovx) were evaluated by histomorphometric, mechanical; and biochemical means. Three days after ovx, suppressed bone formation was seen. This was shown by reduced osteoid volume, osteoblast surface, and bone formation rate in the secondary spongiosa, and a reduced longitudinal growth rate in the growth plate. In addition, the alkaline phosphatase and tartrate-resistant acid phosphatase activity in bone marrow supernatants was suppressed in conjunction with elevated serum sialic acid levels, indicating inflammation. Although estrogen deprivation itself may provoke the inflammatory process, the serum sialic acid level in the ovx group returned to the baseline level within 5 days after surgery, while that of estradiol in the ovx group remained consistently lower. This suggests that surgical stress, not estrogen deprivation, is the primary cause of the inflammatory response shortly after ovx. A significant difference (p < 0.01) between the ovx and sham rats was seen in the osteoclast surface, which peaked on day 7 in the ovx rats. On day 14 postovariectomy, the bone formation rate peaked and remained constant until day 30. In the ovx rats, there was a sustained reduction in the serum albumin level until day 30. Estrogen deprivation may be the primary cause of these changes, because both surgical ovx and medical oophorectomy with gonadotropin-releasing hormone agonist (G(nRHa) reduce the serum albumin level. In numerous studies dealing with changes after ovx in rats, we have observed: 1) a transient reduction in bone formation in relation to inflammatory changes evoked by ovx surgery, and 2) a sustained reduction in the serum albumin level for at least 30 days after ovx that is possibly due to estrogen deprivation.