High plasma levels of CD40 are associated with low coenzyme Q and vitamin E content of low-density lipoprotein in healthy men

OBJECTIVE: There is a growing body of evidence to suggest that low-density lipoprotein (LDL) cholesterol, inflammation and oxidative stress are pivotal in the development of cardiovascular disease, but their interconnections are not well known. The objective of this study was to determine whether immunological activation, reflected by the plasma levels of soluble CD40 (sCD40), interleukin (IL)-1beta, tumor necrosis factor-alpha and IL-6 are associated with the antioxidant potential of LDL particles or with common lipid, immunological or thrombotic markers in 51 young healthy men. MATERIAL AND METHODS: We determined the coenzyme Q level from an oxidized LDL fraction, obtaining the concentration for ubiquinone, which indicates total coenzyme Q levels. RESULTS: The plasma level of sCD40 was negatively correlated with LDL ubiquinone (r=-0.45, p=0.001) and E vitamin (r=-0.37, p=0.008) and positively correlated with plasma concentration of plasminogen activator inhibitor-1 (PAI-1, r=0.52, p=0.002) and caspase-1 (r=0.40, p=0.004). No correlation was detected between sCD40 and plasma lipid or C-reactive protein concentrations. As sCD40 was strongly correlated with the content of LDL ubiquinone and vitamin E, their values were compared according to groups formed by sCD40 tertiles. Analysis of variance showed that there were significant differences in LDL ubiquinone (p<0.0001) and vitamin E (p=0.004) concentrations between sCD40 tertiles. CONCLUSIONS: The data indicate that increased activation of the CD40 system is related to low levels of LDL ubiquinone and vitamin E. This suggests that chronic or increased immunological activation may consume the antioxidant potential of LDL particles.     

Prevalence and significance of vitamin D deficiency and insufficiency among apparently healthy adults

Objective

This study aims to determine the prevalence and significance of vitamin D deficiency and insufficiency among apparently healthy adults.

Design and methods

A total of 123 subjects, 56.9% males and 43.1% females, were recruited from a tertiary care hospital in Karachi, Pakistan. Questionnaires were administered to gather demographics; height, weight, and blood samples were also taken. For staging serum 25OHD, the cutoff values ≤ 50 nmol/L and 50.1–74.9 nmol/L were defined as deficiency and insufficiency, respectively.

Results

The mean vitamin D level in the study subjects was 41.1 ± 9.6 nmol/L. Of them, 90% had low serum 25OHD levels: 69.9% were deficient and 21.1% had insufficient levels of 25OHD. There was a significant negative correlation between serum 25OHD and iPTH levels.

Conclusion

The high prevalence of vitamin D deficiency and insufficiency showed that a high proportion of apparently healthy adults are at risk of developing musculoskeletal and other chronic diseases. Serum iPTH and serum 25OHD levels are better markers of this deficiency as compared to other markers.     

Hereditary and acquired protein S deficiencies are associated with low TFPI levels in plasma

Summary. Background: Protein S and tissue factor pathway inhibitor (TFPI) act together in down‐regulating coagulation. Objective: To investigate the TFPI/protein S system in hereditary and acquired protein S deficiency. Methods: Plasma antigen levels of protein S and full‐length TFPI were determined in heterozygous type I protein S‐deficient individuals (n = 35), patients on oral anticoagulant treatment (OAT) (n = 29), oral contraceptive (OC) users (n = 10) and matched controls. Thrombin generation was determined using calibrated automated thrombography. Results: Full‐length TFPI levels were lower in type I protein S‐deficient individuals (76.8 ± 33.8%) than in age‐ and sex‐matched controls (128.0 ± 59.4%, P < 0.001). Among protein S‐deficient individuals with thrombosis, those on OAT had not only lower total protein S levels (25.7 ± 8.2% vs. 54.7 ± 8.2%, P < 0.001), but also lower full‐length TFPI levels (52.6 ± 15.0% vs. 75.4 ± 22.9%, P = 0.009) than those not on OAT. Similarly, OC users had lower protein S (73.8 ± 11.5% vs. 87.9 ± 10.8%, P = 0.005) and full‐length TFPI levels (73.7 ± 27.7% vs. 106.4 ± 29.2%, P = 0.007) than non‐users. When triggered with tissue factor, plasma from protein S‐deficient individuals generated 3–5‐fold more thrombin than control plasma. The difference was only partially corrected by normalization of the protein S level, full correction requiring additional normalization of the TFPI level. Protein S‐immunodepletion experiments indicated that free protein S and full‐length TFPI form a complex in plasma, and the protein S/TFPI interaction was confirmed by surface plasmon resonance analysis. Conclusions: Full‐length TFPI binds to protein S in plasma and is reduced in genetic and acquired protein S deficiency. The concomitant TFPI deficiency substantially contributes to the hypercoagulable state associated with protein S deficiency.     

Coenzyme Q10 levels are low and associated with increased mortality in post-cardiac arrest patients

AimSurvival after cardiac arrest (CA) is limited by the profound neurologic insult from ischemia–reperfusion injury. Therapeutic options are limited. Previous data suggest a benefit of coenzyme Q₁₀ (CoQ₁₀) in post-arrest patients. We hypothesized that plasma CoQ₁₀ levels would be low after CA and associated with poorer outcomes.MethodsProspective observational study of post-arrest patients presenting to a tertiary care center. CoQ₁₀ levels were drawn 24 h after return of spontaneous circulation (ROSC) and compared to healthy controls. Levels of inflammatory cytokines and biomarkers were analyzed. Primary endpoints were survival to discharge and neurologic status at time of discharge.Results23 CA subjects and 16 healthy controls were enrolled. CoQ₁₀ levels in CA patients (0.28 μmol L^?1, inter-quartile range (IQR): 0.22–0.39) were significantly lower than in controls (0.75 μmol L^?1, IQR: 0.61–1.08, p < 0.0001). The mean CoQ₁₀ level in CA patients who died was significantly lower than in those who survived (0.27 vs 0.47 μmol L^?1, p = 0.007). There was a significant difference in median CoQ₁₀ level between patients with a good vs poor neurological outcome (0.49 μmol L^?1, IQR: 0.30–0.67 vs 0.27 μmol L^?1, IQR: 0.21–0.30, p = 0.02). CoQ₁₀ was a statistically significant predictor of poor neurologic outcome (adjusted p = 0.02) and in-hospital mortality (adjusted p = 0.026).ConclusionCoQ₁₀ levels are low in human subjects with ROSC after cardiac arrest as compared to healthy controls. CoQ₁₀ levels were lower in those who died, as well as in those with a poor neurologic outcome.     

Carotid intima-media thickness is not associated with homocysteine and vitamin D levels in obstructive sleep apnea

Obstructive sleep apnea syndrome (OSA) is associated with increased vascular morbidity. Accelerated atherosclerosis might be one of the most important mechanisms linking OSA with the development of vascular disorders. Homocysteine (HCY) and vitamin D has been associated with atherogenesis. The aim of this study was to assess a possible association between the levels of HCY and vitamin D and the carotid intima-media thickness (cIMT), which is a known marker for subclinical atherosclerosis in patients with OSA. We prospectively enrolled 110 patients with the history of snoring, who underwent standard overnight polysomnography. Clinical characteristics of the population were recorded on admission and blood samples were obtained in the fasting condition following morning. Extracranial cIMT measurements were performed according to the standardized scanning protocol. A significant correlation was found between cIMT and apnea-hypopnea index (r?=?.276, p?=?.006), age (r?=?.486, p?r?=?.377, p?r?=?.274, p?=?.006) and history of stroke (r?=?.251, p?=?.012). We failed to find any significant correlation between cIMT and the levels of HCY (r?=?.036, p?=?.724) or vitamin D (r?=?.027, p?=?.800). In conclusion, our data suggest that the association of cIMT with the severity of OSA can be influenced by multiple metabolic consequences of OSA including traditional and non-traditional risk factors. HCY and vitamin D do not seem to play a superior role in this process.     

Lymphocyte abnormality associated with HLA-B8 in healthy young adults

We have reported that abnormal lymphocyte function in Sjogren's syndrome occurs almost exclusively in patients with HLA-B8. We now report that most clinically normal individuals with this antigen have a similar impairment of cellular immunity. This finding suggests that the lymphocyte abnormality in Sjogren's syndrome is not secondary to the disease process or medication and might have primary etiological significance. The lymphocyte abnormality is expressed as a decreased proliferative response to suboptimally stimulating concentrations of phytohemagglutinin (PHA) and concanavalin A (Con A). In contrast, the response to optimally stimulating concentrations of PHA and Con A is unaffected. The imparied mitogen responsiveness appears to be intrinsic to the T lymphocytes, as it can be demonstrated in purified T cell preparations.     

Serum levels of 25-hydroxyvitamin D in adults and elderly humans after a prophylactic dose of vitamin D2

Vitamin D2 was administered orally as a single dose (2 mg) to 19 elderly subjects and 17 young adults. The maximum elevation of serum 25-hydroxyvitamin D was significantly greater in young than in elderly subjects. To evaluate intestinal absorption we also measured serum levels of vitamin D2 5 h after the given dose. A vitamin A absorption test was also performed simultaneously. Small differences between young and old subjects were seen with respect to serum vitamin D2 or vitamin A increments. In both groups the serum level of 25-hydroxyvitamin D was still elevated above initial level 60 days after a dose was given. No side effects, nor any change in serum calcium ion activity were noted during this period. These results speak in favour of the use of intermittent large doses of vitamin D2 as a prophylaxis against vitamin D deficiency in the elderly.     

Coenzyme Q10 levels are low and may be associated with the inflammatory cascade in septic shock

Introduction  

Mitochondrial dysfunction is associated with increased mortality in septic shock. Coenzyme Q10 (CoQ10) is a key cofactor in the mitochondrial respiratory chain, but whether CoQ10 is depleted in septic shock remains unknown. Moreover, statin therapy may decrease CoQ10 levels, but whether this occurs acutely remains unknown. We measured CoQ10 levels in septic shock patients enrolled in a randomized trial of simvastatin versus placebo.