Urinary neopterin and total neopterin measurements allow monitoring of oxidative stress and inflammation levels of knee and hip arthroplasty patients

Knee and hip arthroplasty are common surgeries within an aging population. Some data has suggested that knee arthroplasty is more traumatic to the body than hip arthroplasty due to the increased complexity and load bearing nature of the joint. Here, we compare the stress of the two surgeries by measuring urinary neopterin and total neopterin as biomarkers of oxidative stress and inflammation. Urinary neopterin and total neopterin (neopterin + 7,8-dihydroneopterin) levels were analysed in 28 knee and 22 hip arthroplasty patients pre- and post-operatively to determine oxidative stress and inflammation levels. Total neopterin was 31.1% higher with knee arthroplasty (p<0.05). Urinary neopterin was 32.8% higher in the knee arthroplasty group versus hips. The increase in neopterin and total neopterin following a post-surgical decrease in levels was significant in both groups. Levels of neopterin and total neopterin were varied between patients, but all increased following surgery and subsided by day 28. The increased levels of urinary neopterin and total neopterin from knee arthroplasty indicate that knee osteoarthritis and arthroplasty is a more significant trauma to the body than hip osteoarthritis and arthroplasty surgery. This is also shown by faster inflammatory resolution following hip arthroplasty.

Cell-Mediated Immune Ontogeny Is Affected by Sex but Not Environmental Context in a Long-Lived Primate Species

Ecoimmunology conceptualizes the role of immunity in shaping life history in a natural context. Within ecoimmunology, macroimmunology is a framework that explains the effects of habitat and spatial differences on variation in immune phenotypes across populations. Within these frameworks, immune ontogeny—the development of the immune system across an individual life span—has received little attention. Here, we investigated how immune ontogeny from birth until adulthood is affected by age, sex, and developmental environment in a long-lived primate species, the bonobo. We found a progressive, significant decline of urinary neopterin levels, a marker for the cell-mediated immune response, from birth until 5 years of age in both sexes. The overall pattern of age-related neopterin changes was sex-specific, with males having higher urinary neopterin levels than females in the first 3 years of life, and females having higher levels than males between 6 and 8 years. Environmental condition (zoo-housed vs. wild) did not influence neopterin levels, nor did age-related changes in neopterin levels differ between environments. Our data suggest that the post-natal development of cell-mediated immune ontogeny is sex-specific but does not show plasticity in response to environmental conditions in this long-lived primate species. This indicates that cell-mediated immune ontogeny in the bonobo follows a stereotypic and maybe a genetically determined pattern that is not affected by environmental differences in pathogen exposure and energy availability, but that sex is an important, yet often overlooked factor shaping patterns of immune ontogeny. Investigating the causes and consequences of variation in immunity throughout life is critical for our understanding of life-history evolution and strategies, mechanisms of sexual selection, and population dynamics with respect to pathogen susceptibility. A general description of sex-specific immune ontogeny as done here is a crucial step in this direction, particularly when it is considered in the context of a species’ ecology and evolutionary history.

Urinary neopterin of wild chimpanzees indicates that cell-mediated immune activity varies by age, sex, and female reproductive status

The study of free-living animal populations is necessary to understand life history trade-offs associated with immune investment. To investigate the role of life history strategies in shaping proinflammatory cell-mediated immune function, we analyzed age, sex, and reproductive status as predictors of urinary neopterin in 70 sexually mature chimpanzees (Pan troglodytes) at Ngogo, Kibale National Park, Uganda. In the absence of clinical signs of acute infectious disease, neopterin levels significantly increased with age in both male and female chimpanzees, as observed in humans and several other vertebrate species. Furthermore, males exhibited higher neopterin levels than females across adulthood. Finally, females with full sexual swellings, pregnant females, and post-reproductive females, the oldest individuals in our sample, exhibited higher neopterin levels than lactating females and cycling females without full swellings. Variation in females’ neopterin levels by reproductive status is consistent with post-ovulatory and pregnancy-related immune patterns documented in humans. Together, our results provide evidence of ample variation in chimpanzee immune activity corresponding to biodemographic and physiological variation. Future studies comparing immune activity across ecological conditions and social systems are essential for understanding the life histories of primates and other mammals.

Dynamic Effects of CAM Techniques on Inflammation and Emotional States: An Integrative Single-Case Study on a Breast Cancer Survivor

Background: This study on a breast cancer survivor investigated how episodic practice of various complementary and alternative medicine (CAM) techniques affected the dynamics of emotional states and urinary neopterin—an inflammation marker. Methods: The 49-year-old female patient (diagnosis: ductal breast carcinoma 5 years before study start, suffering from chronic fatigue and depression) collected her entire urine in 12-hour intervals (from about 8 a.m. to 8 p.m. and from about 8 p.m. to 8 a.m.) for 28 days. The resulting 55 consecutive urine samples were analyzed for neopterin and creatinine levels using HPLC. Also in 12-hour intervals, the patient filled out questionnaires on emotional states and everyday routine, including CAM practice. Weekly, she was interviewed to identify emotionally meaningful everyday incidents, including use of CAM techniques. Time series analysis consisted of ARIMA modeling and cross-correlational analyses. Results: Qualitative evaluation revealed that, with the exception of Tai Chi, all CAM techniques, that is, Jin Shin Jyutsu, music, physiotherapy and energy healing, were experienced as positive. Cross-correlational analyses showed that practice of such CAM techniques was followed first by significant ( P < .05) increases in positive mood and mental activity on the same day (lag 0) and then by decreases in positive mood after a total of 72 to 84 hours (+lag 6) and in mental activity after a total of 84 to 96 hours (+lag 7). Negative mood, by contrast, first decreased on the day of CAM practice (lag 0) and then increased after a total of 84 to 96 hours (+lag 7) following CAM. Moreover, urinary neopterin levels first increased on the day of CAM practice (lag 0) and then decreased after a total of 36 to 48 hours (+lag 3). Similar biphasic effects were also detected for irritation in response to CAM, although only partly significant. Conclusion: Cyclic psychophysiological response patterns following CAM practice were attributable to biopsychosocial feedback mechanisms involving personally meaningful experiences. As lower neopterin levels following CAM point to a health-promoting effect, the patient of this study may have actively contributed to her healing process through episodic CAM practice.

Neopterin and biopterin levels and tryptophan degradation in patients with diabetes

This study aimed to evaluate the possible changes of neopterin, biopterin levels and tryptophan degradation in diabetes and to compare the results within diabetes groups and with healthy subjects. Diabetes mellitus patients and healthy controls were recruited the study. Patients were further subgrouped according to their drug therapy. Serum neopterin concentrations were detected by ELISA. Urinary neopterin, biopterin, serum tryptophan (Trp) and kynurenine (Kyn) levels were detected by HPLC. There was no difference between controls and diabetes patients in serum neopterin, urinary neopterin and biopterin levels (p > 0.05, all). Serum Trp and Kyn levels were significantly different in type 1 diabetes (T1DM) patients compared to controls (p < 0.05, both). Serum neopterin levels were significantly higher in type 2 diabetes patients (T2DM) compared to T1DM (p < 0.05). Urinary biopterin levels of T2DM patients using both metformin and vildagliptin were significantly higher than T1DM patients (p < 0.05). The correlations between serum neopterin and urinary neopterin, Kyn and Kyn/Trp were statistically significant in control and patient groups (p < 0.05, all). The study showed that Kyn/Trp was altered in diabetes patients due to immune modulation. On the other hand, although xenobiotic exposure may change pteridine levels, metformin and/or vildagliptin use in T2DM patients did not have any effect on the measured parameters.

Potential utilization of neopterin measurements in the assessment of pyrexia in metastatic melanoma treated with combined targeted therapy: a case report

In patients with metastatic melanoma the advent of targeted therapy and immune checkpoint inhibitors has transformed the management of advanced and metastatic disease, resulting in improved outcomes. Neopterin is a biomarker of immune activation increased in cancer as well as in other conditions associated with immune activation. We present a case of a patient with advanced metastatic melanoma responding to the combination targeted therapy with dabrafenib and trametinib. The treatment was complicated by a fever that was accompanied by a marked rise in serum and urinary neopterin concentrations. Present case report illustrates not only the efficacy of combined targeted therapy, but also the utilization of neopterin measurements in the diagnosis and monitoring of pyrexia in patients with metastatic malignant melanoma.

Oxidative stress and immune cell activation quantification in sepsis and non-sepsis critical care patients by neopterin/7,8-dihydroneopterin analysis

Introduction: Neopterin and 7,8-dihydroneopterin are used as biomarkers of oxidative stress and inflammation, but the effect of kidney function on these measurements has not been extensively explored. We examine the levels of oxidative stress, inflammation and kidney function in intensive patients and compare them to equivalent patients without sepsis.Methods: 34 Intensive care patients were selected for the study, 14 without sepsis and 20 with. Both groups had equivalent levels of trauma, assessed by SAPS II, SOFA, and APACHE II and III scores. Plasma and urinary neopterin and total neopterin (neopterin + 7,8-dihydroneopterin) values were measured.Results: Neopterin and total neopterin were significantly elevated in urine and plasma for multiple days in sepsis versus non-sepsis patients. Plasma neopterin and total neopterin have decreasing relationships with increased eGFR (p<0.008 and p<0.001, respectively). Plasma/urinary neopterin and total neopterin ratios demonstrate that total neopterin flux is more influenced by eGFR than neopterin, with significantce of p<0.02 and p<0.0002 respectively.Conclusion: Sepsis patients present with greater levels of oxidative stress and immune system activation than non-sepsis patients of equal levels of trauma, as measured by neopterin and total neopterin. eGFR may need to be taken into account when accessing the level of inflammation from urinary neopterin measurements.