Tryptophan degradation in multiple trauma patients: survivors compared with non-survivors

2009 ◽  
Vol 116 (7) ◽  
pp. 593-598 ◽  
Author(s):  
Martin Ploder ◽  
Andreas Spittler ◽  
Katharina Schroecksnadel ◽  
Gabriele Neurauter ◽  
Linda E. Pelinka ◽  
...  
Keyword(s):  
Immune Dysfunction ◽  
Kynurenine Pathway ◽  
Trauma Patients ◽  
Tryptophan Degradation ◽  
Immune System Activation ◽  
System Activation ◽  
Immune Activation Marker ◽  
Multiple Trauma Patients ◽  
Observation Period

Immune dysfunction in trauma patients is associated with immune system activation and inflammation. The cytokine-inducible enzyme IDO (indoleamine 2,3-dioxygenase) initiates the degradation of the essential aromatic amino acid tryptophan via the kynurenine pathway and could contribute to deficient immune responsiveness. Activated IDO is indicated by an increased kyn/trp (kynurenine/tryptophan) ratio. The aim of the present study was to investigate whether tryptophan degradation is associated with outcome in patients post-trauma. Tryptophan and kynurenine concentrations were measured by HPLC in serum specimens of 15 patients post-trauma during 12–14 days of follow-up. Up to five samples within this observation period from each patient were included in this analysis, and a total a 69 samples were available. For further comparisons, concentrations of the immune activation marker neopterin were measured. Compared with healthy controls, the average kyn/trp ratio and kynurenine concentrations were increased in patients, whereas tryptophan concentrations were decreased. During follow-up, increased kyn/trp ratio and kynurenine concentrations (all P<0.001) were observed, whereas the changes in tryptophan concentrations were not significant. Non-survivors had higher kyn/trp ratios and kynurenine concentrations compared with survivors. The kyn/trp ratio correlated with neopterin concentrations (rs=0.590, P<0.001). In conclusion, these results imply that increased tryptophan degradation in patients is due to activated IDO, which most probably is a consequence of a host defence response. These findings support a possible role for IDO in the development of immunodeficiency and death in patients.

Accelerated Tryptophan Degradation in Trauma and Sepsis Patients is Related to Pro-inflammatory Response and to the Diminished in vitro Response of Monocytes

Pteridines ◽  
2009 ◽  
Vol 20 (1) ◽  
pp. 54-61 ◽  
Author(s):  
Martin Ploder ◽  
Andreas Spittler ◽  
Katharina Schroecksnadel ◽  
Gabriele Neurauter ◽  
Linda E. Pelinka ◽  
...  
Keyword(s):  
Kynurenine Pathway ◽  
Tryptophan Degradation ◽  
Immune System Activation ◽  
Tnf Α ◽  
In Vitro Response ◽  
System Activation ◽  
Factor Α

Abstract Immune system activation and inflammation accompanies immune dysfunction in trauma and sepsis patients. Tryptophan degradation via the kynurenine pathway by the cytokine-inducible enzyme indoleamine 2,3-dioxygenase (IDO) could contribute to the deficient responsiveness of immunocompetent cells. Activated IDO in patients after trauma and with sepsis is indicated by an increased kynurenine to tryptophan ratio (kyn/trp), which was found to be associated with poor outcome of patients. In this study, tryptophan and kynurenine concentrations in 18 patients post trauma or with sepsis during 12-14 days of follow up (up to 84 specimens were available) were compared to concentrations of neopterin and cytokines tumor necrosis factor-α (TNF-α) and interleukin- 6 (IL-6) and the in vitro response of lipopolysaccharide-stimulated monocytes. Compared to healthy controls, average kyn/trp and kynurenine, TNF-α, IL-6 and neopterin concentrations were increased in patients, and tryptophan concentrations were decreased. During follow-up, only kyn/trp, kynurenine and neopterin concentrations (all p <0.001) were increasing, whereas the changes of tryptophan, TNF-α and IL-6 concentrations were not significant. Non-survivors presented not only with higher kyn/trp and with higher kynurenine and neopterin concentrations than survivors, but also TNF-α and IL-6 concentrations were higher. Kyn/trp correlated with neopterin (rs = 0.590; p <0.001) and also with TNF-α (rs = 0.374; p <0.01) and IL-6 concentrations (rs = 0.262; p <0.05) and inversely with the in vitro response of stimulated monocytes. Data imply that increased tryptophan degradation in patients post trauma is due to IDO activation. Increased IDO activity most likely represents a result of host defence response in patients, and data support a possible role of IDO to diminish immunoresponsiveness in such patients.

Time-dependence of urinary neopterin, a marker of cellular immune activity.

1988 ◽  
Vol 34 (9) ◽  
pp. 1866-1867 ◽  
Author(s):  
A Auzéby ◽  
A Bogdan ◽  
Z Krosi ◽  
Y Touitou
Keyword(s):  
High Performance ◽  
Early Morning ◽  
Time Of Day ◽  
Immune System Activation ◽  
Total Variability ◽  
System Activation ◽  
Urinary Neopterin ◽  
Cellular Immune ◽  
Urine Specimens

Abstract Neopterin, a marker of cellular immune system activation, is produced by human macrophages after induction by interferon gamma (secreted by T-lymphocytes) and is eliminated mostly in urine. We have documented the circadian rhythm of urinary neopterin in five healthy young men (about 25 years old), using voidings collected during 48 h at fixed 4-h intervals. We repeated the experiment three times, one week apart. Neopterin was measured by high-performance liquid chromatography (HPLC). We clearly show a peak of the excretion of neopterin in the early morning (around 0630 hours +/- 2 h), with total variability (peak-trough difference) reaching 51%. Neopterin is commonly assayed in urinary fractions, so it is imperative to use urine specimens collected at the same time of day--e.g., the first morning urines--to avoid misinterpretation in follow-up of patients.

Long-term Supplementation with Β Vitamins does not Change Plasma Neopterin Concentrations in Demented Patients

Pteridines ◽  
2006 ◽  
Vol 17 (4) ◽  
pp. 135-144 ◽  
Author(s):  
Katharina Schroecksnadel ◽  
Birgit Gruber ◽  
Barbara Frick ◽  
Marcel Jenny ◽  
Maximilian Ledochowski ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Vitamin Supplementation ◽  
Rapid Decline ◽  
Folate Supplementation ◽  
Immune System Activation ◽  
System Activation ◽  
Immune Activation Marker

Abstract Inflammation and immune system activation seem to play an important role in the development and progression of dementia. Also concentrations of immune activation marker neopterin are increased in serum and cerebrospinal fluid of some patients with dementia, and a significant relationship is found between concentrations of neopterin and homocysteine. Β vitamin supplementation is able to rapidly slow-down homocysteine formation in patients. However, no change of neopterin was found within one month of such therapy. In this study, scrum concentrations of neopterin and homocysteine were investigated in 58 patients with Alzheimer's disease (n=30), vascular dementia (n=12) and mild cognitive impairment (n=16) during 1 -3 months of supplementation with Β vitamins (Beneitran compositum®)with monthly increasing dose ( 1 - 6 tablets a day). No change of neopterin concentrations was observed In the patients groups throughout the whole study period (all ρ >0.05). As was reported earlier, a rapid decline of homocysteine concentrations was achieved already within the first month of supplementation (p <0.01 ), however, no further change of homocysteine was observed later on despite accelerated dose of vitamin supplements. Β vitamin supplementation did not influence neopterin concentrations, and also the longer period of supplementation had no effect. The question remains, if solely the lowering of homocysteine concentrations by folate supplementation could have any beneficial effect to modulate the course of dementia when the immunopathogenetic mechanisms are not influenced.

scholarly journals Tryptophan degradation and neopterin levels by aging

Pteridines ◽  
2013 ◽  
Vol 24 (1) ◽  
pp. 33-39 ◽  
Author(s):  
Hande Sipahi ◽  
Gozde Girgin ◽  
Fatma Inanici ◽  
Servet Ariogul ◽  
Gonul Sahin ◽  
...  
Keyword(s):  
Immune Activation ◽  
Neurodegenerative Disorders ◽  
Smoking Habit ◽  
The Elderly ◽  
Tryptophan Degradation ◽  
Immune System Activation ◽  
Age Related ◽  
System Activation ◽  
Cellular Immune

AbstractIncreased neopterin concentrations and altered tryptophan degradation are observed in diseases concomitant with cellular immune activation. This may be involved in the pathogenesis of several age-related disorders such as neurodegenerative disorders, autoimmune diseases, cardiovascular system disorders and malignancies. Therefore, in the present study, the evaluation of immune system activation by determination of tryptophan degradation and serum neopterin levels was carried out in volunteers aged ≥65 and <65 years old. The kynurenine-to-tryptophan ratio was calculated to estimate indoleamine-(2,3)-dioxygenase (IDO) activity. Tryptophan levels in the elderly (53.1±1.6 μmol/L) were lower than individuals under 65 years (61.4±2.2 μmol/L), whereas kynurenine concentrations in geriatrics and adults were 5.0±0.2 μmol/L and 4.3±0.2 μmol/L, respectively (both p<0.05). The kynurenine-to-tryptophan ratio was also significantly higher in geriatrics (92.1±3.2) than adults (73.5±2.8) (p<0.05). Neopterin levels were slightly higher in geriatrics compared to adults under 65 years old (p>0.05). Effects of gender, smoking habit, pathology and drug use on measured parameters were also evaluated. In conclusion, our findings show that aging is associated with immune activation, and immune activation may be induced by the number of existing pathologies as well as the number of drugs used.

scholarly journals Accelerated Tryptophan Degradation Predicts Poor Survival in Trauma and Sepsis Patients

2010 ◽  
Vol 3 ◽  
pp. IJTR.S3983 ◽  
Author(s):  
Martin Ploder ◽  
Andreas Spittler ◽  
Katharina Kurz ◽  
Gabriele Neurauter ◽  
Linda E. Pelinka ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Immune Activation ◽  
Tryptophan Degradation ◽  
Immune System Activation ◽  
Tnf Α ◽  
In Vitro Response ◽  
Immune Activation Marker ◽  
Factor Α

Immune system activation and inflammation accompanies immune dysfunction in trauma and sepsis patients. Immunodeficiency may develop in such patients as one consequence of an activated chronic pro-inflammatory response. According to recent data, degradation of L-tryptophan (TRP) via the kynurenine (KYN) pathway by the cytokine-inducible enzyme indoleamine 2,3-dioxygenase (IDO) could represent an important contributor to the deficient responsiveness of immunocompetent cells. Compared to healthy controls, patients post trauma or with sepsis had increasing KYN concentrations and KYN to TRP ratios (KYN/TRP) whereas TRP concentrations decreased. Likewise, concentrations of cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and of immune activation marker neopterin increased in patients (all p < 0.001). Furthermore in patients KYN/TRP, KYN and neopterin concentrations were further increasing (all p < 0.001), whereas the changes of TRP, TNF-α and IL-6 concentrations were not significant. Compared to the survivors, the non-survivors had a higher concentration of KYN, neopterin, TNF-α and IL-6 as well as a higher KYN/TRP ratio. KYN/TRP correlated with neopterin (p < 0.001) and also with TNF-α (p < 0.01) and IL-6 concentrations (p < 0.05) and inversely with the in vitro response of stimulated monocytes. We conclude that increased TRP degradation in patients post trauma is closely associated with immune activation. Cytokines released during the pro-inflammatory response may induce the activity of IDO and thus accelerate TRP degradation. Thus, increased IDO activity most likely represents a result of host response to pro-inflammation in patients. Data support a possible role of inflammation-induced IDO in the diminished immunoresponsiveness in patients.

scholarly journals Quinolinic acid is associated with cognitive deficits in schizophrenia but not major depressive disorder

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Flurin Cathomas ◽  
Karoline Guetter ◽  
Erich Seifritz ◽  
Federica Klaus ◽  
Stefan Kaiser
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Cognitive Deficits ◽  
Quinolinic Acid ◽  
Kynurenine Pathway ◽  
Group Differences ◽  
Major Depressive ◽  
Immune System Activation ◽  
System Activation ◽  
The Relationship

AbstractTryptophan and its catabolites (TRYCATs) have been suggested to link peripheral immune system activation and central neurotransmitter abnormalities with relevance to the etio-pathophysiology of schizophrenia (SZ) and major depressive disorder (MDD). The relationship to different psychopathological dimensions within these disorders however remains to be elucidated. We thus investigated potential group differences of tryptophan, kynurenine, kynurenic acid, 3-hydroxy kynurenine and quinolinic acid in the plasma of 19 healthy controls (HC), 45 patients with SZ and 43 patients with MDD and correlated plasma proteins with the “motivation and pleasure” dimension and cognition. After correcting for the covariates age, sex, body mass index, smoking and medication, patients with MDD showed lower kynurenine and 3-hydroxy kynurenine levels compared to HC. Quinolinic acid correlated negatively with composite cognitive score in patients with SZ, indicating that more severe cognitive impairments were associated with increased plasma levels of quinolinic acid. No correlations were found in patients with MDD. These results indicate that MDD and SZ are associated with dysregulation of the kynurenine pathway. Quinolinic acid might be specifically implicated in the pathophysiology of cognitive deficits in patients with SZ. Further studies are needed to determine whether TRYCATs are causally involved in the etiology of these neuropsychiatric disorders.

HRA Model for Hypercholesterolemia Based on a Longitudinal Health Database

1998 ◽  
Vol 37 (02) ◽  
pp. 130-133
Author(s):  
T. Kishimoto ◽  
Y. Iida ◽  
K. Yoshida ◽  
M. Miyakawa ◽  
H. Sugimori ◽  
...  
Keyword(s):  
Total Cholesterol ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Model Analysis ◽  
Serum Total Cholesterol ◽  
Hazards Model ◽  
The Mean ◽  
Health Database ◽  
Observation Period

AbstractTo evaluate the risk factors for hypercholesterolemia, we examined 4,371 subjects (3,207 males and 1,164 females) who received medical checkups more than twice at an AMHTS in Tokyo during the period from 1976 through 1991; and whose serum total cholesterol was under 250 mg/dl. The mean follow-up duration was 6.6 years. A self-registering questionnaire was administered at the time of the health checkup. The endpoint of this study was the onset of hypercholesterolemia when the level of serum total cholesterol was 250 mg/dl and over. We compared two prognosis groups (normal and hypercholesterol) in terms of age, examination findings and lifestyle. After assessing each variable, we employed Cox's proportional hazards model analysis to determine the factors related to the occurrence of hypercholesterolemia. According to proportional hazards model analysis, total cholesterol, triglyceride and smoking at the beginning, and hypertension during the observation period were selected in males; and total cholesterol at the beginning and age were selected in females to determine the factors related to the occurrence of hypercholesterolemia.

scholarly journals P014: Incidental findings in trauma whole-body CT scans: a systematic review

CJEM ◽  
2020 ◽  
Vol 22 (S1) ◽  
pp. S69-S69
Author(s):  
V. Tsang ◽  
K. Bao ◽  
J. Taylor
Keyword(s):  
Systematic Review ◽  
Incidental Findings ◽  
Traffic Accidents ◽  
Road Traffic ◽  
Subsequent Treatment ◽  
Whole Body ◽  
Trauma Patients ◽  
Patient Demographics ◽  
Study Results

Introduction: Whole-body computed tomography scans (WBCT) are a mainstay in the work-up of polytrauma or multiple trauma patients in the emergency department. While incredibly useful for identifying traumatic injuries, WBCTs also reveal incidental findings in patients, some of which require further diagnostic testing and subsequent treatment. Although the presence of incidental findings in WBCTs have been well documented, there has been no systematic review conducted to organize and interpret findings, determine IF prevalence, and document strategies for best management. Methods: A systematic review was conducted using MEDLINE, PUBMED, and EMBASE. Specific journals and reference lists were hand-mined, and Google Scholar was used to find any additional papers. Data synthesis was performed to gather information on patient demographics, prevalence and type of incidental findings (IFs), and follow-up management was collected. All documents were independently assessed by the two reviewers for inclusion and any disagreements were resolved by consensus. Results: 1231 study results were identified, 59 abstracts, and 12 included in final review. A mean of 53.9% of patients had at least one IF identified, 31.5% had major findings, and 68.5% had minor findings. A mean of 2.7 IFs per patient was reported for articles that included number of total IFs. The mean age of patients included in the studies were 44 years old with IFs more common in older patients and men with more IFs than women. IFs were most commonly found in the abdominal/pelvic region followed by kidneys. Frequency of follow-up documentation was poor. The most common reported mechanisms of injury for patients included in the study were MVA and road traffic accidents (60.0%) followed by falls from >3m (23.2%). Conclusion: Although there is good documentation on the mechanism of injury, patient demographics, and type of IF, follow-up for IFs following acute trauma admission lacks documentation and follow-up and is an identified issue in patient management. There is great need for systematic protocols to address management of IFs in polytrauma patients.

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