Taurine concentrations in serum of critically injured patients and age- and sex-matched healthy control subjects

1990 ◽  
Vol 52 (4) ◽  
pp. 657-660 ◽  
Author(s):  
J D Paauw ◽  
A T Davis
Author(s):  
Douglas D. Fraser ◽  
Michelle Chen ◽  
Annie Ren ◽  
Michael R. Miller ◽  
Claudio Martin ◽  
...  

Abstract Objectives Severe traumatic brain injury (sTBI) patients suffer high mortality. Accurate prognostic biomarkers have not been identified. In this exploratory study, we performed targeted proteomics on plasma obtained from sTBI patients to identify potential outcome biomarkers. Methods Blood sample was collected from patients admitted to the ICU suffering a sTBI, using standardized clinical and computerized tomography (CT) imaging criteria. Age- and sex-matched healthy control subjects and sTBI patients were enrolled. Targeted proteomics was performed on plasma with proximity extension assays (1,161 proteins). Results Cohorts were well-balanced for age and sex. The majority of sTBI patients were injured in motor vehicle collisions and the most frequent head CT finding was subarachnoid hemorrhage. Mortality rate for sTBI patients was 40%. Feature selection identified the top performing 15 proteins for identifying sTBI patients from healthy control subjects with a classification accuracy of 100%. The sTBI proteome was dominated by markers of vascular pathology, immunity/inflammation, cell survival and macrophage/microglia activation. Receiver operating characteristic (ROC) curve analyses demonstrated areas-under-the-curves (AUC) for identifying sTBI that ranged from 0.870-1.000 (p≤0.005). When mortality was used as outcome, ROC curve analyses identified the top 3 proteins as vWF, WIF-1, and CSF-1. Combining vWF with either WIF-1 or CSF-1 resulted in excellent mortality prediction with AUC of 1.000 for both combinations (p=0.011). Conclusions Targeted proteomics with feature classification and selection distinguished sTBI patients from matched healthy control subjects. Two protein combinations were identified that accurately predicted sTBI patient mortality. Our exploratory findings require confirmation in larger sTBI patient populations.


2018 ◽  
Vol 314 (2) ◽  
pp. H180-H187 ◽  
Author(s):  
U. W. Iepsen ◽  
G. W. Munch ◽  
C. K. Ryrsø ◽  
N. H. Secher ◽  
P. Lange ◽  
...  

Sympathetic vasoconstriction is blunted in exercising muscle (functional sympatholysis) but becomes attenuated with age. We tested the hypothesis that functional sympatholysis is further impaired in chronic obstructive pulmonary disease (COPD) patients. We determined leg blood flow and calculated leg vascular conductance (LVC) during 1) femoral-arterial Tyramine infusion (evokes endogenous norepinephrine release, 1 µmol·min−1·kg leg mass−1), 2) one-legged knee extensor exercise with and without Tyramine infusion [10 W and 20% of maximal workload (WLmax)], 3) ATP (0.05 µmol·min−1·kg leg mass−1) and Tyramine infusion, and 4) incremental ATP infusions (0.05, 0.3, and 3.0 µmol·min−1·kg leg mass−1). We included 10 patients with moderate to severe COPD and 8 age-matched healthy control subjects. Overall, leg blood flow and LVC were lower in COPD patients during exercise ( P < 0.05). Tyramine reduced LVC in both groups at 10-W exercise (COPD: −3 ± 1 ml·min−1·mmHg−1and controls: −3 ± 1 ml·min−1·mmHg−1, P < 0.05) and 20% WLmax(COPD: −4 ± 1 ml·min−1·mmHg−1and controls: −3 ± 1 ml·min−1·mmHg−1, P < 0.05) with no difference between groups. Incremental ATP infusions induced dose-dependent vasodilation with no difference between groups, and, in addition, the vasoconstrictor response to Tyramine infused together with ATP was not different between groups (COPD: −0.03 ± 0.01 l·min−1·kg leg mass−1vs. controls: −0.04 ± 0.01 l·min−1·kg leg mass−1, P > 0.05). Compared with age-matched healthy control subjects, the vasodilatory response to ATP is intact in COPD patients and their ability to blunt sympathetic vasoconstriction (functional sympatholysis) as evaluated by intra-arterial Tyramine during exercise or ATP infusion is maintained.NEW & NOTEWORTHY The ability to blunt sympathetic vasoconstriction in exercising muscle and ATP-induced dilation in chronic obstructive pulmonary disease patients remains unexplored. Chronic obstructive pulmonary disease patients demonstrated similar sympathetic vasoconstriction in response to intra-arterial Tyramine during exercise and ATP-induced vasodilation compared with age-matched healthy control subjects.


2009 ◽  
Vol 37 (3) ◽  
pp. 862-866 ◽  
Author(s):  
J Liang ◽  
Z Zheng ◽  
M Wang ◽  
L Han ◽  
Z Zheng ◽  
...  

There are several reports of myeloperoxidase (MPO) playing an important role in acute coronary syndromes (ACS). Interleukin-17 (IL-17) is a pro-inflammatory cytokine produced by activated CD4 T cells that has a chemotactic and activating effect on neutrophils. It has also been shown that IL-17 recruits neutrophils via the release of C-X-C chemokines. The roles of MPO and IL-17 in ACS, however, have not been established. This study measured plasma MPO and IL-17 levels in 10 patients with ACS, 11 age- and sex-matched patients with stable angina and 12 healthy control subjects. Plasma MPO and IL-17 levels were significantly elevated in ACS patients compared with the patients with stable angina and the healthy control subjects. In addition, plasma MPO levels correlated with plasma IL-17 levels in all study participants. It is concluded that MPO and IL-17 are powerful indicators of acute coronary inflammation, however the data set was very small, so larger prospective studies are required.


2021 ◽  
Vol 17 ◽  
Author(s):  
Yu-Feng Qing ◽  
Quan-Bo Zhang ◽  
Fei Dai ◽  
Yu-Qin Huang ◽  
Jian-Xiong Zheng ◽  
...  

Background: Previous studies demonstrated that MicroRNA-146a (miR-146a) plays an important role in the regulation of autoinflammatory diseases including primary gout. The G/C polymorphism (rs2910164) in the precursor sequence of miR-146a caused its stem region to change from G: U to C: U,which can contribute to the susceptibility of human diseases. however, no genetic relevance studies of miR-146a gene polymorphisms to gout have been reported by now. Objective: The purpose of this study was to analyze the association between the miR-146a rs2910164 genetic polymorphism and the susceptibility of Chinese Han population to primary gout. Method:1130 Chinese Han participants (including 606 primary gout patients and 524 gender and age-matched healthy control subjects) were recruited and the 5'exonuclease TaqMan® technology was used to perform miR-146a rs2910164 genotyping. Method: 1130 Chinese Han participants (including 606 primary gout patients and 524 gender and age-matched healthy control subjects) were recruited and the 5'exonuclease TaqMan® technology was used to perform miR-146a rs2910164 genotyping. Result: After statistical analysis, no significant differences were observed between gout patients and healthy controls in genotype and allele frequency. Conclusion: Our results indicate that there is no evidence for the involvement of the miR-146a rs2910164 polymorphisms in susceptibility to primary gout in the Chinese Han population.


Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5571-5571 ◽  
Author(s):  
Feng Jin ◽  
Michelle Robeson ◽  
Huafeng Zhou ◽  
Grace Hisoire ◽  
Srini Ramanathan

Abstract Background Idelalisib (IDELA) is a potent competitive inhibitor of the ATP binding site of the PI3K p110s catalytic domain, which has been shown to be prominently expressed in cells of hematopoietic origin. IDELA is metabolized primarily by aldehyde oxidase to form GS-563117 and to a lesser extent by CYP3A and UGT1A4. Based on mass balance study of IDELA, the majority of the radioactive dose administered in healthy subjects was recovered in feces (∼78%).  The objective of the present study was to evaluate the pharmacokinetics and safety of IDELA and GS-563117 in subjects with moderate or severe hepatic impairment following administration of a single oral dose of IDELA. Methods Eligible subjects were enrolled into 2 cohorts that included subjects with moderate or severe hepatic dysfunction as categorized by the ChildPugh-Turcotte (CPT) classification system and healthy controls matched for age, gender, and body mass index. Each subject received a single oral dose of IDELA at 150 mg under fed condition. Blood samples for IDELA and GS-563117 were collected over 6 days post-dose and were measured using a validated LC/MS/MS method. The ratio and 90% confidence interval of the least squares geometric means of PK exposure parameters in the hepatic impairment group(s) versus matched controls were calculated, with clinically relevant exposure change defined as ≥ two-fold increase. Safety assessments were performed throughout the study. Results A total of 32 subjects were enrolled in the study. The majority of subjects were white (87.5%) males (71.9%) and median age was 52 years. Study treatments were generally well tolerated. The majority of the treatment-emergent AEs (TEAE) were assessed as Grade 1 in severity. The only TEAE reported in more than 1 subject was headache (5 subjects overall; 2 subjects with moderate hepatic impairment and 3 healthy subjects). Most treatmentemergent laboratory abnormalities were Grade 1 or 2 in severity. Single oral doses of IDELA 150 mg were well tolerated in subjects with hepatic impairment and in healthy matched controls. IDELA Cmax was generally comparable in the subjects with moderate (CPT Class B) or severe (CPT Class C) hepatic impairment relative to healthy matched control subjects, while mean AUC was higher (58% to 60%). GS-563117 exposures were lower in subjects with moderate and severe hepatic impairment relative to matched healthy control subjects, likely due to lower formation in the setting of liver impairment. Overall, the observed changes in mean exposures of IDELA and GS-563117 are not considered to be clinically relevant. Exploratory analyses indicated no relevant relationships between the IDELA or GS-563117 plasma exposures and CPT score for subjects with moderate or severe hepatic impairment. Conclusion No clinically relevant changes in IDELA and GS-563117 exposures were observed in subjects with moderate or severe hepatic impairment versus matched healthy control subjects. Single oral doses of IDELA 150 mg were well tolerated. Disclosures: Jin: Gilead Sciences: Employment, Equity Ownership. Robeson:Gilead Sciences: Employment, Equity Ownership. Zhou:Gilead Sciences: Employment, Equity Ownership. Hisoire:Gilead Sciences: Employment, Equity Ownership. Ramanathan:Gilead Sciences: Employment, Equity Ownership.


Author(s):  
A. Filla ◽  
R.F. Butterworth ◽  
A. Barbeau

SUMMARY:Pyruvate dehydrogenase (PDH) activity was measured in platelets from 10 patients with Friedreich's ataxia, and 10 age-matched healthy control subjects. Both total PDH and active PDH activity were measured. There were no significant differences between the two groups.


Urology ◽  
1999 ◽  
Vol 53 (4) ◽  
pp. 800-805 ◽  
Author(s):  
Wallace W Dinsmore ◽  
Michael Hodges ◽  
Claire Hargreaves ◽  
Ian H Osterloh ◽  
Michael D Smith ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document