A systematic review and meta-analysis of neopterin in rheumatic diseases

IntroductionNovel biomarkers of inflammation and oxidative stress might enhance the early recognition, management, and clinical outcomes of patients with rheumatic diseases (RDs). We assessed the available evidence regarding the pathophysiological role of neopterin, the oxidation product of 7,8-dihydroneopterin, a pteridine generated in macrophages activated by interferon-γ, by conducting a systematic review and meta-analysis of studies reporting its concentrations in biological fluids in RD patients and healthy controls.MethodsWe searched electronic databases for relevant articles published between inception and 31 August 2023. The risk of bias and the certainty of evidence were assessed using the Joanna Briggs Institute Critical Appraisal Checklist and the Grades of Recommendation, Assessment, Development and Evaluation Working Group system, respectively.ResultsIn 37 studies, when compared to healthy controls, RD patients had significantly higher concentrations of neopterin both in plasma or serum (standard mean difference, SMD=1.31, 95% CI 1.01 to 1.61; p<0.001; moderate certainty of evidence) and in the urine (SMD=1.65, 95% CI 0.86 to 2.43, p<0.001; I2 = 94.2%, p<0.001; low certainty of evidence). The results were stable in sensitivity analysis. There were non-significant associations in meta-regression and subgroup analysis between the effect size and age, male to female ratio, year of publication, sample size, RD duration, C-reactive protein, erythrocyte sedimentation rate, specific type of RD, presence of connective tissue disease, analytical method used, or biological matrix investigated (plasma vs. serum). By contrast, the effect size was significantly associated with the geographical area in studies assessing serum or plasma and with the type of RD in studies assessing urine.DiscussionPending additional studies that also focus on early forms of disease, our systematic review and meta-analysis supports the proposition that neopterin, a biomarker of inflammation and oxidative stress, can be useful for the identification of RDs. (PROSPERO registration number: CRD42023450209).Systematic review registrationPROSPERO, identifier CRD4202345020

Transsulfuration pathway thiols and methylated arginines: the hunter community study

Background: Serum homocysteine, when studied singly, has been reported to be positively associated both with the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine [ADMA, via inhibition of dimethylarginine dimethylaminohydrolase (DDAH) activity] and with symmetric dimethylarginine (SDMA). We investigated combined associations between transsulfuration pathway thiols, including homocysteine, and serum ADMA and SDMA concentrations at population level. Methods: Data on clinical and demographic characteristics, medication exposure, C-reactive protein, serum ADMA and SDMA (LC-MS/MS), and thiols (homocysteine, cysteine, taurine, glutamylcysteine, total glutathione, and cysteinylglycine; capillary electrophoresis) were collected from a sample of the Hunter Community Study on human ageing [n = 498, median age (IQR) = 64 (60–70) years]. Results: Regression analysis showed that: a) age (P = 0.001), gender (P = 0.03), lower estimated glomerular filtration rate (eGFR, P = 0.08), body mass index (P = 0.008), treatment with beta-blockers (P = 0.03), homocysteine (P = 0.02), and glutamylcysteine (P = 0.003) were independently associated with higher ADMA concentrations; and b) age (P = 0.001), absence of diabetes (P = 0.001), lower body mass index (P = 0.01), lower eGFR (P&lt;0.001), cysteine (P = 0.007), and glutamylcysteine (P&lt;0.001) were independently associated with higher SDMA concentrations. No significant associations were observed between methylated arginines and either glutathione or taurine concentrations. Conclusions: After adjusting for clinical, demographic, biochemical, and pharmacological confounders the combined assessment of transsulfuration pathway thiols shows that glutamylcysteine has the strongest and positive independent associations with ADMA and SDMA. Whether this reflects a direct effect of glutamylcysteine on DDAH activity (for ADMA) and/or cationic amino acid transport requires further investigations.</br

Clinical and biochemical correlates of serum L-ergothioneine concentrations in community-dwelling middle-aged and older adults

Background: Despite the increasing interest towards the biological role of L-ergothioneine, little is known about the serum concentrations of this unusual aminothiol in older adults. We addressed this issue in a representative sample of communitydwelling middle-aged and older adults. Methods: Body mass index, estimated glomerular filtration rate, serum concentrations of L-ergothioneine, taurine, homocysteine, cysteine, glutathione, cysteinylglycine, and glutamylcysteine were evaluated in 439 subjects (age 55–85 years) randomly selected from the Hunter Community Study. Results: Median L-ergothioneine concentration in the entire cohort was 1.01 IQR 0.78–1.33 mmol/L. Concentrations were not affected by gender (P = 0.41) or by presence of chronic medical conditions (P = 0.15). By considering only healthy subjects, we defined a reference interval for L-ergothioneine serum concentrations from 0.36 (90% CI 0.31–0.44) to 3.08 (90% CI 2.45–3.76) mmol/L. Using stepwise multiple linear regression analysis L-ergothioneine was negatively correlated with age (rpartial =20.15; P = 0.0018) and with glutamylcysteine concentrations (rpartial =20.13; P = 0.0063). Conclusions: A thorough analysis of serum L-ergothioneine concentrations was performed in a large group of communitydwelling middle-aged and older adults. Reference intervals were established. Age and glutamylcysteine were independently negatively associated with L-ergothioneine serum concentration.</br

Effects of Isolated Systolic Hypertension and Essential Hypertension on Large and Middle-sized Artery Compliance

Systolic hypertension of the elderly is characterized by a reduction in arterial compliance. Whether and to what extent this involves arteries of various structure and size is not well known.To study carotid and radial artery compliance in systolic hypertension of the elderly, compared to essential hypertension and normotension.We investigated 28 elderly patients with systolic hypertension (age 68.6 +/- 1.4 years, mean +/- SE; systolic blood pressure160 mmHg and diastolic blood pressure90 mmHg) plus 17 age-matched patients with essential hypertension and 15 age-matched healthy normotensive subjects. Radial and carotid artery compliance were evaluated using echotracking techniques. In both arteries compliance was assessed statistically and dynamically, i.e. as compliance values throughout the diasto-systolic pressure range. Measurements included intima-media wall thickness of the radial artery.Compared to normotensive subjects, carotid artery compliance was reduced in essential hypertension and more so in systolic hypertension. However, although in both groups radial artery wall thickness was markedly greater than in the normotensive group, radial artery compliance was markedly reduced in systolic hypertension, but unchanged in essential hypertension.In systolic hypertension of the elderly the reduction of arterial compliance is marked in both muscular and large elastic arteries, while in elderly essential hypertensives changes in arterial compliance are more heterogeneous, i.e. only carotid artery compliance is reduced. The different effects of these two types of hypertension on arterial mechanics are visible throughout the physiological range of blood pressure and probably accounted for by different alterations in vessel wall structure

Folic Acid: A Marker of Endothelial Function in Type 2 Diabetes?

Arduino A Mangoni1, Roy A Sherwood2, Belinda Asonganyi2, Emma L Ouldred3, Stephen Thomas4, Stephen HD Jackson31Department of Clinical Pharmacology, Centre for Neuroscience, School of Medicine, Flinders University, Adelaide, SA, Australia; 2Clinical Biochemistry, King&rsquo;s College Hospital, London, UK; 3Department of Health Care of the Elderly, Guy&rsquo;s, King&rsquo;s, and St Thomas&rsquo; School of Medicine, King&rsquo;s College, London, UK; 4Department of Diabetic Medicine, King&rsquo;s College Hospital, London, UKObjectives: Endothelial dysfunction is a common feature of type 2 diabetes. Recent studies suggest that the B-vitamin folic acid exerts direct beneficial effects on endothelial function, beyond the well known homocysteine lowering effects. Therefore, folic acid might represent a novel &ldquo;biomarker&rdquo; of endothelial function. We sought to determine whether plasma levels of folic acid determine endothelial-dependent vasodilation in patients with type 2 diabetes.Methods: Forearm arterial blood flow (FABF) was measured at baseline and during intrabrachial infusion of the endothelial-dependent vasodilator acetylcholine (15 &micro;g/min) and the endothelial-independent vasodilator sodium nitroprusside (2 &micro;g/min) in 26 type 2 diabetic patients (age 56.5 &plusmn; 0.9 years, means &plusmn; SEM) with no history of cardiovascular disease.Results: FABF ratio (ie, the ratio between the infused and control forearm FABF) significantly increased during acetylcholine (1.10 &plusmn; 0.04 vs 1.52 &plusmn; 0.07, p &lt; 0.001) and sodium nitroprusside (1.12 &plusmn; 0.11 vs 1.62 &plusmn; 0.06, p &lt; 0.001) infusions. After correcting for age, gender, diabetes duration, smoking, hypertension, body mass index, microalbuminuria, glycated hemoglobin, low-density lipoprotein cholesterol, and homocysteine, multiple regression analysis showed that plasma folic acid concentration was the only independent determinant (p = 0.037, R2 = 0.22) of acetylcholine-mediated, but not sodium nitroprusside-mediated, vasodilatation.Conclusions: Folic acid plasma concentrations determine endothelium-mediated vasodilatation in patients with type 2 diabetes. These results support the hypothesis of a direct effect of folic acid on endothelial function and the rationale for interventions aimed at increasing folic acid levels to reduce cardiovascular risk.Keywords: folic acid, homocysteine, endothelium, type 2 diabete

Platelet Count and Platelet Indices in Patients with Stable and Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis

Platelets play an important role in the pathophysiology of chronic obstructive pulmonary disease (COPD) by mediating thrombotic, inflammatory, and immune processes in the lung. We conducted a systematic review and meta-analysis of studies investigating the platelet count and three platelet indices, mean platelet volume (MPV), platelet distribution width (PDW), and platelet to lymphocyte ratio (PLR) in stable COPD vs. non-COPD patients and in stable COPD vs. acute exacerbation of COPD (AECOPD) patients (PROSPERO registration number: CRD42021228263). PubMed, Web of Science, Scopus and Google Scholar were searched from inception to December 2020. Twenty-seven studies were included in the meta-analysis, 26 comparing 4,455 stable COPD patients with 7,128 non-COPD controls and 14 comparing 1,251 stable COPD with 904 AECOPD patients. Stable COPD patients had significantly higher platelet counts (weighted mean difference, WMD = 13.39 x1

Patterns of Drug Use and Serum Sodium Concentrations in Older Hospitalized Patients : A Latent Class Analysis Approach

Peer reviewedPublisher PD

Diets high in n-3 fatty acids are associated with lower arterial stiffness in patients with rheumatoid arthritis: a latent profile analysis

Supplementation with n-3 fatty acids can influence inflammation and markers of arterial stiffness that are increased in patients with rheumatoid arthritis (RA). However, it is unknown whether specific patterns of dietary fatty acid intake are similarly associated. In a longitudinal study, eighty-six RA patients reported their dietary intake and had arterial stiffness measured using the augmentation index (AIx) at baseline and 8 months. Latent profile analysis (LPA) was performed to characterise patterns of fatty acid intake using sixteen major fatty acids. Models for two to six profiles were compared using the Akaike and Bayesian information criteria. Associations between AIx and the profiles were adjusted for age, sex, disease activity, fish oil supplementation, medications, physical activity and socio-economic status. LPA identified five distinct profiles. Profile 1 subjects (n 7) reported significantly higher intake of palmitoleic acid (16 : 1), arachidonic acid (20 : 4n-6), EPA (20 : 5n-3), DHA (22 : 6n-3) and docosapentaenoic acid (22 : 5n-3) (