scholarly journals Active Pyruvate Dehydrogenase In Platelets From Friedreich's Ataxia Patients

1980 ◽  
Vol 7 (4) ◽  
pp. 417-419 ◽  
Author(s):  
A. Filla ◽  
R.F. Butterworth ◽  
A. Barbeau
Keyword(s):  
Pyruvate Dehydrogenase ◽  
Friedreich’S Ataxia ◽  
Friedreich's Ataxia ◽  
Control Subjects ◽  
Matched Healthy Control ◽  
Healthy Control

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.

scholarly journals Serum and Platelet Lipoamide Dehydrogenase in Friedreich's Ataxia

1978 ◽  
Vol 5 (1) ◽  
pp. 111-114 ◽  
Author(s):  
A. Filla ◽  
R. F. Butterworth ◽  
G. Geoffroy ◽  
B. Lemieux ◽  
A. Barbeau
Keyword(s):  
Standard Deviation ◽  
Normal Control ◽  
Pyruvate Dehydrogenase ◽  
Friedreich’S Ataxia ◽  
Friedreich's Ataxia ◽  
Control Subjects ◽  
Lipoamide Dehydrogenase

SUMMARY:Pyruvate dehydrogenase (PDH), α -keto gluturate dehydrogenase (α -KGDH) and lipoamide dehydrogenase (LAD) were measured in platelets of II patients with typical Friedreich's ataxia and 10 normal control subjects. Serum LAD was also evaluated in the same patients. No statistically significant changes were found in platelets for the group as a whole, although some patients had low values (more than one standard deviation below control mean). Serum LAD was significantly reduced in the patients with Friedreich's ataxia. This was not due to associated diabetes.

Novel severe traumatic brain injury blood outcome biomarkers identified with proximity extension assay

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Douglas D. Fraser ◽  
Michelle Chen ◽  
Annie Ren ◽  
Michael R. Miller ◽  
Claudio Martin ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Severe Traumatic Brain Injury ◽  
Roc Curve ◽  
Vascular Pathology ◽  
Targeted Proteomics ◽  
Control Subjects ◽  
Matched Healthy Control ◽  
Healthy Control ◽  
Age And Sex

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.

scholarly journals Plasma Lipoprotein Lipase and Hepatic Lipase Activities in Friedreich’s Ataxia

1982 ◽  
Vol 9 (2) ◽  
pp. 191-194 ◽  
Author(s):  
D. Blache ◽  
D. Bouthillier ◽  
A. Barbeau ◽  
J. Davignon
Keyword(s):  
Lipoprotein Lipase ◽  
Hepatic Lipase ◽  
Friedreich’S Ataxia ◽  
Friedreich's Ataxia ◽  
Hepatic Triglyceride ◽  
Normal Range ◽  
Triglyceride Lipase ◽  
Plasma Triglycerides ◽  
Control Subjects ◽  
Hepatic Triglyceride Lipase

SUMMARY:Plasma triglycerides although within the normal range have been shown to be higher in Friedreich’s ataxia than in control subjects. To determine whether this difference could be ascribed to a reduced catabolism of triglyceride-rich lipoproteins, the activities of lipoprotein lipase (LPL) and hepatic triglyceride lipase (HL), released into plasma after an heparin injection, were measured in 13 cases of Friedreich’s ataxia and 14 control subjects of comparable signs. LPL was found to be significantly lower in the ataxic patients. Moreover about half of the cases clustered below the normal range for both lipase activities. This subgroup of Friedreich’s patients had significantly higher plasma triglycerides than those with normal lipase activities. Further studies are needed to relate these findings to other characteristics of the disease.

scholarly journals Muscle α-adrenergic responsiveness during exercise and ATP-induced vasodilation in chronic obstructive pulmonary disease patients

2018 ◽  
Vol 314 (2) ◽  
pp. H180-H187 ◽  
Author(s):  
U. W. Iepsen ◽  
G. W. Munch ◽  
C. K. Ryrsø ◽  
N. H. Secher ◽  
P. Lange ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Control Subjects ◽  
Matched Healthy Control ◽  
Copd Patients ◽  
Sympathetic Vasoconstriction ◽  
Functional Sympatholysis ◽  
Healthy Control

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.

scholarly journals Platelet Taurine Uptake in Spinocerebellar Degeneration

1978 ◽  
Vol 5 (1) ◽  
pp. 119-123 ◽  
Author(s):  
A. Filla ◽  
R. F. Butterworth ◽  
G. Geoffroy ◽  
B. Lemieux ◽  
A. Barbeau
Keyword(s):  
Normal Control ◽  
Friedreich’S Ataxia ◽  
Friedreich's Ataxia ◽  
Spinocerebellar Degeneration ◽  
Control Subjects ◽  
Uptake Pattern ◽  
Transport Defect ◽  
Taurine Uptake ◽  
Kinetics Of

SUMMARY:The uptake of 14C-laurine was studied in the platelets of 20 ataxic patients and 20 age-matched normal control subjects. No significant differences were found in uptake or kinetics of taurine between the two groups of subjects. If a transport defect in taurine exists in Friedreich's ataxia, it is not present in all tissues. Preliminary indication was obtained in favor of heterogenity of the uptake pattern between ataxic individuals.

scholarly journals Friedreich's Ataxia 1979: An Overview

1979 ◽  
Vol 6 (2) ◽  
pp. 311-319 ◽  
Author(s):  
A. Barbeau
Keyword(s):  
Linoleic Acid ◽  
Pyruvate Dehydrogenase ◽  
Phenotypic Expression ◽  
Clinical Work ◽  
Friedreich’S Ataxia ◽  
Friedreich's Ataxia ◽  
High Density Lipoproteins ◽  
Cholesteryl Esters ◽  
Cooperative Study ◽  
Lipoamide Dehydrogenase

SummaryThis overview summarizes the investigations carried out during the second part of Phase Two of the Quebec Cooperative Study of Friedreich's Ataxia. These investigations outline in more details the fundamental role played by an abnormality in the fatty acid composition (deficient linoleic acid, 18:2) of the cholesterol esters of high density lipoproteins (HDL) in the phenotypic expression of the disease. They postulate a defective incorporation of linoleic acid to surface phos-phatidylcholine of chylomicrons and consequent relative and absolute decreases in lipoproteinprotein components because of overpacking with defective cholesteryl esters. Secondarily to these changes, the postulated lack of activation of the lipoamide dehydrogenase (LAD) of the pyruvate dehydrogenase (PDH) complex could result in slow pyruvate oxidation, glucose intolerance, deficient synthesis of acetylcholine, and depletion of glutamic and aspartic acid pools. In parallel, abnormal phosphatidyl-choline molecules could be incorporated to membranes, resulting in specific defects in some functions of these membranes, including transport of calcium and I or taurine and myelinization. The framework of an understanding of Friedreich's ataxia is now available, but much fundamental and clinical work remains to be done to fill in and prove each one of these postulated steps.

No association of microRNA-146a rs2910164 polymorphism and risk of primary gout development in Chinese Han populations: a case-control study

2021 ◽  
Vol 17 ◽  
Author(s):  
Yu-Feng Qing ◽  
Quan-Bo Zhang ◽  
Fei Dai ◽  
Yu-Qin Huang ◽  
Jian-Xiong Zheng ◽  
...  
Keyword(s):  
Case Control Study ◽  
Chinese Han Population ◽  
Chinese Han ◽  
Han Population ◽  
Control Subjects ◽  
Primary Gout ◽  
Matched Healthy Control ◽  
Gender And Age ◽  
Healthy Control ◽  
Control Study

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.

The Pharmacokinetics and Safety Of Idelalisib In Subjects With Moderate Or Severe Hepatic Impairment

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5571-5571 ◽  
Author(s):  
Feng Jin ◽  
Michelle Robeson ◽  
Huafeng Zhou ◽  
Grace Hisoire ◽  
Srini Ramanathan
Keyword(s):  
Oral Dose ◽  
Hepatic Impairment ◽  
Healthy Subjects ◽  
Severe Hepatic Impairment ◽  
Employment Equity ◽  
Control Subjects ◽  
Matched Healthy Control ◽  
Healthy Control ◽  
Equity Ownership ◽  
Oral Doses

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.

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