Neopterin Levels Research Articles

Higher Cerebrospinal Fluid Soluble Urokinase-type Plasminogen Activator Receptor, But Not Interferon γ-inducible Protein 10, Correlate With Higher Working Memory Deficits.

We hypothesized that the induction of monocyte activation biomarkers, especially soluble urokinase-type plasminogen activator receptor (suPAR) and interferon γ-inducible protein 10 (IP-10), is lower in HIV-1C than HIV-1B, owing to a defective Tat cysteine dimotif (C30S). A total of 68 paired cerebrospinal fluid (CSF) and blood samples from people with HIV (PWH), free of CNS opportunistic infections, from a Southern Brazil outpatient HIV clinic were evaluated such as HIV-1B subtype (n = 27), HIV-1C (n = 26), other (n = 15), and 19 HIV-negative controls. The levels of suPAR, IP-10, neopterin, and β2 microglobulin (β2m) in the CSF and serum were quantified using different immunoassays. Overall, in PWH, increases in CSF suPAR, CSF/serum suPAR, and CSF/serum β2m correlated with worse working memory deficits (r = 0.303, 0.353, and 0.289, respectively, all P < 0.05). The medians of IP-10, suPAR, neopterin, and β2m in CSF and serum and the CSF/serum ratio and suPAR index were comparable between the HIV-1B and HIV-1C subtypes. CSF IP-10 and neopterin and serum IP-10 and suPAR levels were higher in PWH than the HIV-negative controls (P = 0.015, P = 0.001, P < 0.0001, and P < 0.001, respectively). The serum β2m level was higher in HIV-associated dementia than neuropsychologically normal or asymptomatic (P = 0.024). We observed that higher levels of CSF suPAR and the suPAR quotient correlated with worse working memory deficit. Elevated levels of monocyte activation were similar in both HIV-1 B and C subtypes, providing no evidence of reduced neuropathogenicity of HIV-1 subtype C Tat compared with subtype B.

Comparison of the levels of neopterin, CRP, and IL-6 in patients infected with and without SARS-CoV-2

BackgroundNeopterin (NP) is a biomarker for activated cellular immunity and is elevated in diseases including viral and bacterial infections, autoimmune diseases, and cancer. However, the clinical assessment of neopterin has not been used for these disorders because the physiological significance of measuring NP is obscure. It would be important to compare the NP profiles with those of other inflammation markers especially in relatively early phase of patients to reveal the significance of NP measurements in pathological states. MethodsPlasma NP, biopterin, CRP, and IL-6 levels were measured in 46 patients with Coronavirus Disease 2019 (COVID-19) and 23 patients with non-COVID-19 disorders. The correlations between these markers were analyzed in the COVID-19 and non-COVID-19 patients independently. ResultsThe NP levels were significantly higher in the COVID-19 patients than in the non-COVID-19 patients, while biopterin, CRP and IL-6 were not changed significantly. The NP levels were found to show a weak negative correlation against the days after onset in the COVID-19 patients (rs = –0.348, p = 0.0192), suggesting that the elevation of NP would be an early event of viral infection. Correlations between NP and CRP, or between NP and IL-6 in COVID-19 patients were weaker than that between CRP and IL-6. ConclusionsThe elevation of NP levels was supposed to be distinct from those of CRP and IL-6 in relatively early and mild COVID-19 patients. Our data suggest that NP is produced at the early phase of infection by different signaling pathways and/or cells from those of CRP and IL-6. Further study on the signaling pathway to induce NP is expected.

Pharmacological correction of immunometabolic disorders in patients with endometrioma along with chronic inflammatory diseases of the genital tract

The objective: to determine the markers of the inflammatory process, development and implementation of methods for pharmacological correction of immunometabolic disorders in patients with endometrioma on the background of chronic inflammatory processes of the pelvic organs. Materials and methods. A complex clinical and laboratory examination of 90 patients with ovarian endometrioma on the background of chronic inflammation was carried out. Of these patients, the comparison group included 45 patients who received basic therapy (antibacterial drugs cefotaxime and metronidazole, vitamin therapy (B vitamins), combined oral contraceptives with dienogest). Patients in the main group (45 women) received basic anti-inflammatory and antibiotic therapy, together with drugs that improve microcirculation and have systemic and local anti-inflammatory and thrombolytic properties (tissue antihypoxant, deproteinized hemoderivative drug from calf blood and local two-component thrombolytic in suppositories) and dienogest and vitamin D3. The control group included 30 gynecologically healthy women.ELISA-method was used to determine tumor necrosis factor-α (TNF-α) level, interleukins (IL) 1β, 4, 10, interferon-γ in blood serum and cervical mucus, immunoglobulins A, M, G in blood serum, and C-reactive protein (CRP), neopterin and 25-hydroxyvitamin-D3. Results. We determined that in patients with endometrioma on the background of chronic pelvic inflammatory disease at the systemic and local levels there are an increased level of proinflammatory cytokines and decreased level of anti-inflammatory cytokines, as well as increased IFN-γ level, increased CRP – in 8.2 times, and neopterin – 2.7 times (p &lt;0.05) relative to healthy women. The use of the proposed treatment program leads to normalize of IgG level and anti-inflammatory cytokine indices within a month. The level of CRP was significantly reduced in the main group, both in blood serum and cervical mucus. There was a decrease neopterin level in patients of the main group by 1.8 times after the treatment.Conclusions. Additional criteria for diagnosis of the inflammatory process in patients with endometrioma are a significant increase level of pro-inflammatory cytokines (TNF-α, IL-1β) and a decrease level of anti-inflammatory (IL-4, IL-10) cytokines, as well as a significant increase of C-reactive protein and neopterin.Studies suggest that the proposed therapy has a corrective effect on altered parameters of metabolic and immune status, which explains the importance of use in this group of patients the antibacterial therapy together with immunomodulatory, antiviral and metabolic drugs.

Fecal biomarkers of environmental enteric dysfunction and associated factors among children aged 24\u201359 months in east Dembiya district, northwest Ethiopia

BackgroundEnvironmental enteric dysfunction is a subclinical intestinal disorder characterized by gut inflammation accompanied by morphological changes, such as blunted villi and crypt hyperplasia. This is a common illness in low and middle-income countries. However, environmental enteric dysfunction evidence is limited in Ethiopia. Accordingly, this study was conducted to measure fecal biomarkers of environmental enteric dysfunction and associated factors among children aged 24–59 months in rural northwest Ethiopia.MethodsA community-based cross-sectional study was employed among 235 randomly selected children in a rural setting of the east Dembiya district. Stool samples were collected without fixative and analyzed for fecal biomarkers of environmental enteric dysfunction (Alpha-1-antitrypsin, neopterin, and myeloperoxidase) using commercial enzyme-linked immunosorbent assay kits and analyzed for intestinal parasites using wet mount and Kato-Katz techniques. Child behaviors related with exposure to enteropathogens, condition of the living environment and socio-demographic information were collected using interviewer-administered questionnaire and structure observation. We fitted multivariable linear regression model to assess the association between environmental factors and concentration of fecal biomarkers of environmental enteric dysfunction in the stool. Statistically significant associations were declared based on adjusted betas with the corresponding 95% confidence interval and p-value < 0.05.ResultsThe median concentration of fecal markers of environmental enteric dysfunction was 350 μg/ml for Alpha-1-antitrypsin, 3320.2 ng/ml for myeloperoxidase, and 1562 nmol/l for neopterin. The median concentration of Alpha-1-antitrypsin among 161 (68.5%), myeloperoxidase among 168 (71.5%), and neopterin among 188 (80%) of the stool samples were above the normal values in non-tropical settings. Moreover, 100 (42.6%) of the children had high EED disease activity score (above the median score). The elevated concentrations of fecal biomarkers of gut inflammation and the high EED disease activity score were significantly associated with open defecation practice, mouthing of soil contaminated materials, Escherichia coli (E. coli) contamination of drinking water, E. coli contamination of foods, E. coli contamination of soil, and intestinal parasites.ConclusionOverall, Alpha-1-antitrypsin, myeloperoxidase, and neopterin levels among the children in the studied region were highly elevated in comparison to populations in high-income countries. Moreover, the EED disease activity score in significant proportion of children was high, suggesting widespread intestinal inflammation and increased intestinal permeability. Extensive E. coli contamination of the living environment (drinking water, ready-to-eat foods, and courtyard soil), hygiene and sanitation behaviors (such as open defecation and mouthing of soil contaminated materials), and a high burden of intestinal parasites were identified as factors associated with the elevated concentration of fecal biomarkers of environmental enteric dysfunction. Parental care to children to avoid mouthing of soil contaminated materials and other risky behaviors that increase exposure enteric infections, and protecting the living environment (water, food and soil) from fecal contamination are important.

CSF neopterin and beta-2-microglobulin as inflammation biomarkers in newborns with hypoxic-ischemic encephalopathy.

Inflammation plays a crucial role in the pathogenesis of hypoxic-ischemic encephalopathy (HIE). The aim of this study was to measure inflammation in HIE through an analysis of CSF neopterin and β2-microglobulin and to study the association with brain injury as shown by MRI findings and neurodevelopmental outcomes. CSF biomarkers were measured in study patients at 12 and 72 h. Brain injury was evaluated by MRI, and neurodevelopmental outcomes were assessed at 2-3 years of life. An adverse outcome was defined as the presence of motor or cognitive impairment. Sixty-nine HIE infants were included. Median values of neopterin and β2-microglobulin paralleled the severity of HIE. Adverse outcomes were associated with early neopterin and β2-microglobulin values, late neopterin values, and the neopterin percentage change between the two samples. A cutoff value of 75% neopterin change predicted adverse outcomes with a specificity of 0.9 and a sensitivity of 0.75. CSF neopterin and β2-microglobulin are elevated in HIE, indicating the activation of inflammation processes. Infants with adverse neurodevelopmental outcomes show higher levels of CSF neopterin and β2-microglobulin. The evolution of neopterin levels provides a better predictive capacity than a single determination. Brain inflammation in newborns with HIE could be measurable through the analysis of CSF neopterin and β2-microglobulin, both of which are associated with neurodevelopmental outcomes. Our study introduces two inflammatory biomarkers for infants with HIE that seem to show a more stable profile and are easier to interpret than cytokines. CSF neopterin and β2-m may become clinical tools to monitor inflammation in HIE and might eventually be helpful in measuring the response to emerging therapies.

Neopterin Relates to Lifetime Depression in Older Adults With HIV on Suppressive Antiretroviral Therapy.

Chronic inflammation contributes to the pathogenesis of depression in persons with HIV (PWH). Neopterin, a biomarker of HIV-related immune activation that partially normalizes with antiretroviral therapy (ART), correlates with major depressive disorder (MDD) and subclinical depressive symptoms in persons without HIV and acutely infected, young PWH. The sensitivity of neopterin, however, to both lifetime and current depression is poorly understood in older PWH on suppressive ART. Participants were 70 PWH and 35 persons without HIV (HIV-) who were at least 50 years old and completed standardized neurobehavioral and neuromedical assessments. Depressive symptoms in the past 2 weeks, measured with the Beck Depression Inventory-II (BDI-II), and lifetime MDD diagnoses, defined as meeting Diagnostic and Statistical Manual of Mental Disorders-IV criteria for a depressive episode at any point in one's lifetime, were separately modeled as a function of plasma neopterin levels in the full sample and by HIV serostatus. Compared with HIV- adults, PWH had higher neopterin levels (P < 0.001) and BDI-II scores (P < 0.01) and were more likely to have lifetime MDD (P < 0.01). Higher neopterin related to lifetime MDD, but only in PWH, even after controlling for clinically relevant comorbidities and treatment factors in logistic regression (odds ratio = 3.11, P = 0.002). Higher neopterin correlated with higher BDI-II scores in the full sample (rs = 0.25; P = 0.010), but not within either group (PWH: rs = 0.03, P = 0.819; HIV-: rs = 0.09, P = 0.588). Neopterin was associated with lifetime MDD, but not current depressive symptoms in older PWH on suppressive ART. This may reflect a legacy of inflammation-related disruptions to amino acid metabolism and neurotransmitter synthesis, similar to prior observations. Identification of biopsychosocial and resilience factors underlying the null association between neopterin and current depression in older PWH is warranted.

Clinical comparative study assessing the effect of ivabradine on neopterin and NT-Pro BNP against standard treatment in chronic heart failure patients

PurposeHeart rate reduction (HR) is a cornerstone in heart failure therapy as it improves patient outcomes. The aim of this study is to evaluate short-term effect of ivabradine on NT-Pro BNP and neopterin in heart failure patients and assess the association between HR and these biomarkers.MethodsSixty patients on standard heart failure therapy were randomly allocated into ivabradine group (n = 30) and non-ivabradine group (n = 30). Ivabradine 5 mg twice daily was given for 3 months. Lipid profile and kidney functions were performed and blood samples for NT-Pro BNP and neopterin were analysed at baseline and after 3 months of intervention in both groups.ResultsThere was a significant improvement in NYHA class in ivabradine group (p < 0.001). Ejection fraction was improved in ivabradine and non-ivabradine groups after intervention (p < 0.001), with a greater improvement in ivabradine group (p = 0.026). Heart rate was reduced in ivabradine group (p < 0.001) and non-ivabradine group (p < 0.001) yet greater reduction was seen in ivabradine group (p < 0.001). Serum creatinine and blood urea nitrogen were reduced in ivabradine group (Scr: p = 0.001, BUN: p = 0.001). NT-Pro BNP and neopterin levels significantly decreased in ivabradine group (NT-Pro BNP: p < 0.001, neopterin p < 0.001). Significant positive correlation was found between HR and biomarker levels after intervention (NT-Pro BNP: r = 0.475, p < 0.001, neopterin: r = 0.384, p = 0.002).ConclusionIvabradine therapy reduced levels of both biomarkers which correlated well with HR. Biomarker levels might provide a tool for assessing ivabradine effectiveness in HF.Trial registrationDate: June 26, 2020. Identifier: NCT04448899. Link: Ivabradine in Patients with Congestive Heart Failure—Full Text View—ClinicalTrials.gov.

Neopterin as a biomarker showing risks of developing pathology in bronchi and lungs among workers who have occupational contacts with industrial aerosols

Our research goal was to estimate neopterin level in blood serum of workers occupationally exposed to industrial aerosols with predominantly fibrogenic effects; to establish a relationship between this level and workers’ age, working experience in hazardous working conditions, spirometric parameters and the level of C-reactive protein. We also aimed to assess neopterin as a possible biomarker showing risks of the developing inflammatory process in the bronchi and lungs at its early stage. Our observation covered the following groups: workers employed at a metallurgic plant who had occupational contacts with industrial aerosols (exposure factors included welding and silicon-containing aerosols with predominantly fibrogenic effects in concentrations exceeding maximum permissible ones in workplace air); people suffering from chronic obstructive pulmonary disease of occupational etiology (COPD OE) in their post-exposure period; workers who didn’t have any occupational contacts with industrial aerosols. We determined neopterin contents in blood serum with ELISA test using “Neopterin ELISA” reagent kit (IBL, Hamburg). Elevated neopterin levels were detected in blood serum of 56.1 % workers who were occupationally exposed to industrial aerosols and 53.3 % of patients with COPD OE; we also found a direct correlation between levels of neopterin and interferon gamma. Only 18.7 % workers without any occupational contacts with industrial aerosols had elevated neopterin levels in their blood serum and there were no authentic correlations between these levels and interferon gamma contents in this group. Workers who were occupationally exposed to industrial aerosols had a more apparent increase in the average level of neopterin at an age younger than 40 years and working experience shorter than 20 years in comparison with workers without any such exposure. Neopterin can be used as a potential sensitive biomarker showing risks of an early inflammatory reaction in the lungs occurring in workers who are occupationally exposed to industrial aerosols. People with elevated neopterin levels in blood, especially those who are occupationally exposed to industrial aerosols, can be recommended to have their bronchi and lungs monitored in dynamics.

Неоптерин как биомаркер риска развития бронхолегочной патологии у работающих в контакте с промышленными аэрозолями Главные вкладки Просмотр(активная вкладка) Редактировать

Our research goal was to estimate neopterin level in blood serum of workers occupationally exposed to industrial aerosols with predominantly fibrogenic effects; to establish a relationship between this level and workers’ age, working experience in hazardous working conditions, spirometric parameters and the level of C-reactive protein. We also aimed to assess neopterin as a possible biomarker showing risks of the developing inflammatory process in the bronchi and lungs at its early stage. Our observation covered the following groups: workers employed at a metallurgic plant who had occupational contacts with industrial aerosols (exposure factors included welding and silicon-containing aerosols with predominantly fibrogenic effects in concentrations exceeding maximum permissible ones in workplace air); people suffering from chronic obstructive pulmonary disease of occupational etiology (COPD OE) in their post-exposure period; workers who didn’t have any occupational contacts with industrial aerosols. We determined neopterin contents in blood serum with ELISA test using “Neopterin ELISA” reagent kit (IBL, Hamburg). Elevated neopterin levels were detected in blood serum of 56.1 % workers who were occupationally exposed to industrial aerosols and 53.3 % of patients with COPD OE; we also found a direct correlation between levels of neopterin and interferon gamma. Only 18.7 % workers without any occupational contacts with industrial aerosols had elevated neopterin levels in their blood serum and there were no authentic correlations between these levels and interferon gamma contents in this group. Workers who were occupationally exposed to industrial aerosols had a more apparent increase in the average level of neopterin at an age younger than 40 years and working experience shorter than 20 years in comparison with workers without any such exposure. Neopterin can be used as a potential sensitive biomarker showing risks of an early inflammatory reaction in the lungs occurring in workers who are occupationally exposed to industrial aerosols. People with elevated neopterin levels in blood, especially those who are occupationally exposed to industrial aerosols, can be recommended to have their bronchi and lungs monitored in dynamics.

The presence of Neopterin in the sera of a sample of Iraqi acromegalic patients (Type 2 diabetics and nondiabetics)

Back ground: Acromegaly is a rare endocrine disease; its incidence is 4-6 million per year, while its prevalence is 40-60 million per year. They are separating acromegaly from gigantism that occurs before growth plates are closed. Neopterin is a systemic adaptive immune activation biomarker produced upon interferon-gamma (IFN-γ) stimulation by monocyte-derived macrophages and dendritic cells. Eighty acromegalic patients (50% diabetic acromegalic and 50% nondiabetic acromegalic) and forty healthy control groups were enrolled in the study to find out the level of Neopterin and insulin-like growth factor-1 in the sera of the study population; the results showed both molecules (neopterin and Insulin-like growth factor-1 were found to be high in acromegalic subjects when there is concomitant diabetes, and insulin-like growth factor-1 correlates positively with total cholesterol and neopterin. At the same time, neopterin correlates positively with HbA1c. This study was aimed to find out the difference in neopterin level in diabetic acromegalic versus n0n-diabetic acromegalic patients; Eighty acromegalic subjects were enrolled in across sectional study by measuring the neopterin level in the sera of diabetics and nondiabetics as 39 have diabetes while the remaining 41 patients are nondiabetic. Neopterin is high among diabetic acromegalic patients when compared with nondiabetic acromegalic subjects. Insulin-like growth factor-1 correlates positively with neopterin and total cholesterol; (4) Conclusions: Across sectional-study enrolling eighty acromegalic patients registered in the National Diabetes Center. Thus they were subdivided into two groups: - diabetic and nondiabetic the level of neopterin was found to be among diabetic versus nondiabetics.

Liquid chromatography method with tandem mass spectrometry and fluorescence detection for determination of inflammatory biomarkers in gingival crevicular fluid as a tool for diagnosis of periodontal disease

The new ultra-high performance liquid chromatography method with tandem mass spectrometry and fluorescence detection allowing fast, selective, and high-throughput analysis of neopterin, kynurenine, tryptophan, and creatinine in gingival crevicular fluid (GCF) has been optimized. Defining the pathophysiology of periodontal disease and identification of potential diagnostic test for active periodontitis remains a significant challenge in the field of oral disease diagnosis. Analysis of GCF provides a non-invasive means of evaluating the role of the host response in periodontal disease. In addition, the analysis of GCF provides an information about current inflammation level of sampled site/tooth. Determination of GCF inflammatory biomarkers such as neopterin, kynurenine, and tryptophan can contribute to diagnosis, evaluation of treatment, and progression of periodontal diseases such as gingivitis and periodontitis. The separation of target analytes was carried out using a column Kinetex™ Polar C18 100 Å, (100 × 3.0 mm) packed with 2.6 µm core-shell particles applying an elution with a gradient formed from 0.2% aqueous formic acid and 90% aqueous acetonitrile. Kynurenine, tryptophan, and creatinine were detected using mass spectrometry with electrospray ionization to improve the sensitivity while neopterin was detected using fluorescence detection. The separation of these four substances was achieved after using a very simple sample preparation technique convenient for small amount of biological sample. Only less than 20 µL sample was needed and the separation was completed in 4 min. MS/MS analysis was performed using multiple reaction monitoring (MRM) under a positive ionization mode. Deuterium labeled internal standard was used for the more precise quantification. The lower limits of quantification (LLOQ) for target analytes were 0.50 × 10–3 µmol/L for neopterin, 0.10 µmol/L for kynurenine, and 0.20 µmol/L for tryptophan and creatinine. The within-run and between-run accuracy were in a range of 96.67–114.77% for all quality controls and LLOQ of all analytes. Matrix effect, extraction recovery, and stability testing have all been investigated. The method was tested with real-life samples using GCF collected from patients suffering from periodontitis and from healthy controls. Neopterin levels in patients were significantly higher (P = 0.020) than in healthy subjects and indicate good potential of this method for using in evaluation of periodontal pathogenesis and healing outcomes following a treatment.

Study of serum neopterin in children with attention deficit hyperactivity disorder and autistic spectrum disorder: Fayoum Governorate, Egypt

BackgroundThere is evidence supporting that cellular immunity may play a role in the pathophysiology of autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). Neopterin, a pteridine mainly synthesized by activated macrophages, is a marker of inflammation, immune system activation that may be involved in the pathophysiology of both disorders.MethodsFifty drug-naïve patients were diagnosed according to DSM-5 (25 with ASD, 25 with ADHD), in addition to 25 healthy volunteers matched in age and gender with the patients were included. The CARS, Conners’ scales used to assess the severity of the disorders, respectively. Serum neopterin level was measured using ELISA technique for all participants.ResultsStatistically nonsignificant difference in mean neopterin level between control and both patients groups with significant negative correlation between neopterin level and younger ages in ASD group were found. Statistically nonsignificant difference also was found between its levels among subtypes of ADHD as well and with the degree of ASD symptoms severity.ConclusionsThere was no statistically significant difference between serum neopterin level in ADHD, ASD patients groups and control group reference.

Clinical Study On the Relationship Between Neopterin and Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is a reproductive endocrine and metabolic disorder. To offer new research direction for polycystic ovary syndrome (PCOS), including its pathogenesis and treatment, this research explores the relationship between neopterin (NPT) and polycystic ovary syndrome. 40 cases with PCOS were selected in the reproductive medicine clinics of the Second Affiliated Hospital of Shandong First Medical University as PCOS group from January 2017 to December 2018. 40 cases with normal pregnancy plan were treated as non-PCOS group, whose menstruation is from 25 days to 35 days. We divided the two groups into two subgroups separately according to their body mass index (BMI): the obese one with BMI≥25kg/m2and non-obese one with BMI&lt;25kg/m2 . The expression levels of triglycerides (TG), total cholesterol (TC), fasting insulin (FINS), C-reactive protein (CRP), neutrophil (N), NPT and interleukin-6 (IL-6) in PCOS group were higher than non-PCOS group. CRP, NPT and IL-6 in the obese group were increased than the non-obese group in the pairwise comparison of its subgroups whether in PCOS group or non-PCOS group. In the analysis of linear correlation, NPT was positively correlated with TG, TC, WBC, N, CRP, FINS, IL-6 and TNF-α (P&lt;0.01). Multivariate Stepwise regression analysis found that FINS and IL-6 was the two most important factors. The expression of NPT in PCOS patients was higher than nonPCOS. NPT maybe play a significant role in the development of PCOS

Oxidative stress and motion sickness in one crew during competitive offshore sailing

Competitive Offshore Ocean Sailing is a highly demanding activity in which subjects are exposed to psychophysical stressors for a long time. To better define the physiological adaptations, we investigated the stress response of subjects exposed to 3-days long ocean navigation with disruption of circadian rhythms. 6 male subjects were involved in the study and provided urine and saliva samples before setting sail, during a single day of inshore sailing, during 3-days long ocean navigation, and at the arrival, to measure oxidative stress, cortisol, nitric oxide metabolites (NOx) and metabolic response. Motion Sickness questionnaires were also administered during the navigation. The crew suffered a mean weight loss of 1.58 kg. After the long navigation, a significant increase in ROS production and decrease in total antioxidant capacity and uric acid levels were observed. Lipid peroxidation, NO metabolites, ketones, creatinine, and neopterin levels were also increased. Furthermore, a significant increase in cortisol levels was measured. Finally, we found a correlation between motion sickness questionnaires with the increase of NOx, and no correlation with cortisol levels. Physical and psychological stress response derived from offshore sailing resulted in increased oxidative stress, nitric oxide metabolites, and cortisol levels, unbalanced redox status, transient renal function impairment, and ketosis. A direct correlation between motion sickness symptoms evaluated through questionnaires and NOx levels was also found.

Correlations between cerebrospinal fluid biomarkers, neurocognitive tests, and resting-state electroencephalography (rsEEG) in patients with HIV-associated neurocognitive disorders

HIV-associated neurocognitive disorders (HAND) are highly prevalent in people living with HIV (PLWH) despite successful treatment with combination antiretroviral therapy (cART). HAND pathogenesis is complex and definitive surrogate biomarkers are not clearly defined. Brain function has been assessed through the evaluation of cortical source rhythms with delta waves associated with neurological impairment. The aim of this study was to assess the correlation between EEG cortical sources, cerebrospinal fluid (CSF) biomarkers, and neurocognitive tests in PLWH with HAND. PLWH with HAND without significant comorbidities were enrolled. Baseline rsEEG-LORETA waves, CSF biomarkers (t-tau, p-tau, β-amiloid42, neopterin, S100β), and neurocognitive tests were correlated and compared through non-parametric tests (Spearman's rho and Mann-Whitney); data are presented as medians (interquartile ranges). Fifty-four patients were enrolled. Median time of suppressed HIV-RNA and CD4+ T-lymphocyte were 10years (5.5-15) and 691/uL (477-929). Thirty-nine participants (72%) underwent CSF collection: abnormal biomarkers were found in a small percentage. Only neopterin showed a statistically significant correlation with delta activity [parietal (rho 0.579; p < 0.001), occipital (rho 0.493; p = 0.007), and global sources (rho 0.464 p = 0.011)]. Seven patients (12.9%) showed an abnormal neopterin level (> 1.5ng/mL) with significantly higher delta source activity compared to the ones with in-range concentrations. We observed a statistically significant correlation between working memory test Trail Making B with both CSF neopterin levels and delta waves (p values < 0.05). In a small sample of PLWH with HAND, we observed that higher CSF neopterin levels were associated with higher EEG delta waves and worse working memory tests.

THE DIAGNOSTIC VALUE OF ANTIBODIES TO NEUTROPHIL ELASTASE IN NAFLD AND COPD PATIENTS

This article presents data on the influence of enzymatic activity of serum on the processes of liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD) and chronic obstructive pulmonary disease (COPD). Clinical, biochemical, immunological research methods and enzyme-linked immunosorbent assay (ELISA) were used in the work. All patients were determined for the degree of liver fibrosis using a non-invasive method – Fibromax. It was found that in patients with NAFLD and COPD with frequent exacerbations, the levels of CRP, IL-6, TNF-α and neopterin are significantly higher than in patients who had one or no exacerbation of COPD. Stably high levels of systemic inflammation markers of TNF-α, neopterin, CRP lead to the activation of TGF-β, which increases with the deepening stage of liver fibrosis. The average values of IgG antibodies to neutrophil elastase significantly increase depending on the stage of fibrotic changes in the liver and the activity of inflammatory changes in it, with the highest concentration in fibrosis F2. In F3-4 fibrosis, the levels of antibodies to elastase are reduced, although they remain higher than the control values. Significant increase IgG antibody levels to neutrophil elastase depending on the stage of fibrosis and the activity of inflammatory changes indicates the role of serum enzymatic activity in the mechanisms of formation of more severe stages of NAFLD and can be considered as additional diagnostic markers.

Association of IL-6 promoter polymorphism hotspots (-174G/C and -572G/C) with cardiovascular disease risk factors.

Cardiovascular disease (CVD) is the leading cause of death globally, despite the recent advancements in clinical research. Early diagnosis of CVD and prevention of future complications are important for the management of CVD. In the present study, we determined the genotypic linkage of interleukin-6 (IL-6) promoters with the clinical, biochemical, and inflammatory markers of CVD in the Saudi population. The study consisted of 89 patients (male and female) with CVD who were admitted at the King Abdulaziz university hospital, Jeddah, Saudi Arabia. The biochemical parameters were evaluated using an automated chemistry analyzer, and inflammatory markers were measured using specific enzyme-linked immunosorbent assay (ELISA) kits. For genotypic analysis, Sanger sequencing was performed. We observed a statistically significant association (p < 0.05) between GG (66.29%), GC (30.34%), and CC (3.37%) genotypes at the -174G/C (rs1800795) hotspot and neopterin levels. However, the genotypes at the -572G/C (rs1800796) hotspot did not show any association with age, gender, obesity, diabetes, hypertension, dyslipidemia, smoking, and coronary artery status. In addition, no significant association was observed with biochemical and inflammatory markers, namely fasting blood sugar, glycated hemoglobin A1c, creatinine, total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, IL-6, and C-reactive protein. The comparison between different possible genotypic groups and CVD risk factors showed a statistically significant (p < 0.05) association between the male gender and HDL with GG, rs1800795 group vs. GC, rs1800796 group. Similarly, neopterin level was also found to be significantly (p < 0.05) associated with the genotypes GC, rs1800795, and GG, rs1800796. Additionally, the male gender (p < 0.01), age (p < 0.05), serum creatinine (p < 0.001), and neopterin (p < 0.05) were found to be significantly associated with GG, rs1800795 + GG, rs1800796, GC, rs1800795 + GC, and rs1800796 GC. The direct association of neopterin level with IL-6 promoter polymorphism at -174G/C (rs1800795) hotspot indicated the role of inflammation in CVD pathogenesis in the Saudi population.

Immunologic Change over 72 Weeks Following Raltegravir- Versus Efavirenz-Based Therapy in HIV/HCV-Coinfected Individuals in Vietnam.

The impact of HIV antiretroviral therapy (ART) on immune dysregulation associated with hepatitis C virus (HCV)/HIV coinfection is incompletely understood. We serially assessed monocyte activation (neopterin, sCD14, and sCD163) and T cell activation (HLA-DR, CD38) and immune exhaustion [program cell death protein 1 (PD1), TIGIT] in HIV/HCV-coinfected individuals who participated in a randomized trial performed in Vietnam designed to assess the hepatotoxicity of raltegravir (RAL)- versus efavirenz (EFV)-based therapy when used as first-time ART in combination with tenofovir disoproxil fumarate and emtricitabine. Baseline pre-ART values were compared with those from ART-naive HIV-monoinfected and HIV-seronegative individuals. Before ART, HIV/HCV-coinfected individuals had higher levels of neopterin, sCD14, and sCD163, and increased frequencies of CD38+HLA-DR+, PD1+, and TIGIT+ CD4 and CD8 T cells compared with ART-naive HIV-monoinfected or HIV-seronegative individuals (all p < .01). Most parameters did not normalize despite 72 weeks of ART. In particular sCD163 persisted at high levels. Improvement over 72 weeks in fibrosis as assessed by FibroScan® correlated with reductions in plasma sCD163 and in the frequencies of T cell activation, single PD1+, TIGIT+, and dual PD1+TIGIT+ CD8 T cells. A nonsignificant tendency toward more favorable effects on monocyte and T cell immune activation and on T cell exhaustion were seen with RAL-compared with EFV-based therapy. The initiation of ART in HIV/HCV-coinfected individuals is associated with incomplete improvement in monocyte and T cell immune activation and exhaustion, which was associated with some corresponding improvement in liver fibrosis.

ПОВЫШЕНИЕ ЭФФЕКТИВНОСТИ ЛЕЧЕНИЯ БОЛЬНЫХ ОСТРОПРОГРЕССИРУЮЩИМ ИНФИЛЬТРАТИВНЫМ И ДИССЕМИНИРОВАННЫМ ТУБЕРКУЛЕЗОМ ЛЕГКИХ С ПОМОЩЬЮ КОРРЕКЦИИ СОДЕРЖАНИЯ НЕОПТЕРИНА И RANTES

Objective: to improve effectiveness of treatment for acute progressive destructive infiltrative or disseminated pulmonary TB using individualized pathogenetic therapy based on neopterin and RANTES levels in blood serum. Materials and methods. We studied neopterin and RANTES levels in 36 patients with infiltrative or disseminated TB with lung cavities and acute progression at the time of diagnosis, 37 patients without signs of acute progression, and 30 healthy donors. Results. Neopterin and RANTES levels were higher in patients with signs of acute progression of destructive pulmonary TB; they were referred to diagnostic criteria for acute progressive course of TB at neopterin levels more than 26.5 nmol/L and RANTES levels more than 83 387 pg/mL. Low levels of neopterin (less than 9.6 nmol/L) were in patients with advanced acute progressive pulmonary TB and severe comorbidities; it was prognostically unfavourable as well as at RANTES levels more than 83 387 pg/mL. Neopterin and RANTES levels were decreasing at slow rates in patients with acute progression of TB at the time of diagnosis. Administration of gamma-D-glutamyl-tryptophan sodium to patients with high levels of neopterin and glutamyl-cysteinyl-glycine disodium to patients with low levels of neopterin fostered recovery of neopterin and RANTESlevels by the 6th month of treatment in patients with acute progressive TB; it correlated with positive treatment outcomes and cure within 24–36 months in 87% of patients vs 19% of patients, which did not receive personalized pathogenetic therapy. Conclusion. The study demonstrated effectiveness of individualized immunotherapy in the treatment for acute progressive pulmonary TB. Keywords: TB, neopterin, RANTES, acute progressive TB, immunotherapy

Determination of neopterin in urine of industrial workers by HPLC.

This study aimed to determine neopterin levels in the urine of industrial workers by the high-performance liquid chromatography method. Intra- and inter-day precision values for neopterin in urine were less than 3.14, and accuracy (relative error) was better than 3.00%. The limits of detection and quantification of neopterin were 0.3 and 1.0 ng/mL, respectively. Also, the developed method was applied to real samples to determine the neopterin levels in the urines of industrial workers, who have been exposed to various chemicals such as formaldehyde, heavy metals and thinners. Urine neopterin levels of industrial workers including auto painters, bodywork and furniture workers were statistically compared with healthy volunteers. The highest and lowest values of urinary neopterin for industrial workers were obtained 908.96 and 119.86 μmol/mol, respectively. Our investigation demonstrates that there is a meaningful difference in urinary neopterin levels between the workers and the control groups (P<0.05). Workers in the auto paint, body and furniture business may have been exposed to a toxic environmental exposure in their occupation. As a result, an increase in the concentration of neopterin in the urine may be important in the diagnosis and treatment of various diseases.