Cardiorespiratory fitness, oxygen uptake efficency slope and endothelial function in male adolescents

Cardiorespiratory fitness (CRF) is a independent risk factor for CVD and all-cause mortality. Maximal oxygen uptake (VO2max), is considered the gold standard measurement of CRF. Due to its effort dependency, a true plateau in VO2 during incremental exercise is often not attained, particularly in overweight and obese pediatric populations 1. The oxygen uptake efficiency slope (OUES) has been proposed as an objective and effort independent submaximal measure of cardiopulmonary reserve. Studies in healthy and obese children have reported a strong positive relation between OUES and VO2max. Children with high CRF have higher OUES values than those with low CRF 2. Furthermore, improvements in CRF following exercise training, are associated with restoration of endothelial function (EF) in obese children 3. The purpose of this study was to examine the relation between OUES, VO2max and EF in healthy male adolescents. ad

Effects of minor Gaelic football match play on markers of muscle damage, delayed onset muscle soreness and muscle function

Purpose: This study examined the alterations in circulating creatine kinase (CK) levels, leukocyte trafficking, delayed onset muscle soreness (DOMS), muscle function in response to Gaelic football match-play in male adolescents. Methods: Participants (n=30, age 17.41 ± 0.78 yr, height 176.42 ± 7.13 cm, and mass 72.03 ± 6.49 kg) played a specially organised 15-a-side Gaelic Football game of 60 min duration. Blood samples were taken before the game, immediately post-game (Post), 12 h postgame (12 h), 36 h post game (36 h) and 60 h post game (60 h). Subjective muscle soreness, sprint performance and peak force were measured post, 12 h, 36 h and 60 h. Heart rate and movement patterns were continuously measured throughout the game using telemetry and GPS tracking, respectively. Heavy to severe impacts were classified as acceleration G-forces ³ 7 recorded via portable accelerometry. Results: Participants covered an average distance of 6.1 ± 1.1 km during match play. The majority (72%) of the distance involved walking and jogging and high speed and maximal activity accounted for 10% of the total distance. There was a total of 155 impacts ≥ 7 G-forces. C K levels were significantly higher than baseline immediately post-game and 12 h and returned to pregame values at 36 h. Compared to pre-match values circulating leukocytes and granulocytes were significantly higher than pre-game values immediately after the game and decreased significantly below pre-games values at 12h, 36 h and 60 h. Circulating lymphocyte numbers were significantly decreased below immediately post game and at 36 h post game. There was no change in the number of circulating monocytes. Compared to pre-game values, there was a significant decrease in peak force at 12 h and 60 h and a significant increase in 5 m and 20 m sprint times at 12 h, 36 h and 60 h. DOMS scores were significantly higher than pre-games values at 12 h and 36 h and lower (p<0.05) than pre-game values at 60 h. There was no significant relation between impacts and CK levels. Conclusion: Competitive Gaelic football match results in significant changes in CK levels, DOMS, leukocyte trafficking, peak force and 5 m and 20 m sprint performance

HCV and the hepatic lipid pathway as a potential treatment target

Atherosclerosis has been described as a liver disease of the heart. The liver is the central regulatory organ of lipid pathways but since dyslipidaemias are major contributors to cardiovascular disease and type 2 diabetes rather than liver disease, research in this area has not been a major focus for hepatologists. Virus-host interaction is a continuous co-evolutionary process involving the host immune system and viral escape mechanisms. One of the strategies HCV has adopted to escape immune clearance and establish persistent infection is to make use of hepatic lipid pathways. This review aims to: update the hepatologist on lipid metabolism; review the evidence that HCV exploits hepatic lipid pathways to its advantage; discuss approaches to targeting host lipid pathways as adjunctive therapy

Infection with the hepatitis C virus causes viral genotype-specific differences in cholesterol metabolism and hepatic steatosis

Lipids play essential roles in the hepatitis C virus (HCV) life cycle and patients with chronic HCV infection display disordered lipid metabolism which resolves following successful anti-viral therapy. It has been proposed that HCV genotype 3 (HCV-G3) infection is an independent risk factor for hepatocellular carcinoma and evidence suggests lipogenic proteins are involved in hepatocarcinogenesis. We aimed to characterise variation in host lipid metabolism between participants chronically infected with HCV genotype 1 (HCV-G1) and HCV-G3 to identify likely genotype-specific differences in lipid metabolism. We combined several lipidomic approaches: analysis was performed between participants infected with HCV-G1 and HCV-G3, both in the fasting and non-fasting states, and after sustained virological response (SVR) to treatment. Sera were obtained from 112 fasting patients (25% with cirrhosis). Serum lipids were measured using standard enzymatic methods. Lathosterol and desmosterol were measured by gas-chromatography mass spectrometry (MS). For further metabolic insight on lipid metabolism, ultra-performance liquid chromatography MS was performed on all samples. A subgroup of 13 participants had whole body fat distribution determined using in vivo magnetic resonance imaging and spectroscopy. A second cohort of (non-fasting) sera were obtained from HCV Research UK for comparative analyses: 150 treatment naïve patients and 100 non-viraemic patients post-SVR. HCV-G3 patients had significantly decreased serum apoB, non-HDL cholesterol concentrations, and more hepatic steatosis than those with HCV-G1. HCV-G3 patients also had significantly decreased serum levels of lathosterol, without significant reductions in desmosterol. Lipidomic analysis showed lipid species associated with reverse cholesterol transport pathway in HCV-G3. We demonstrated that compared to HCV-G1, HCV-G3 infection is characterised by low LDL cholesterol levels, with preferential suppression of cholesterol synthesis via lathosterol, associated with increasing hepatic steatosis. The genotype-specific lipid disturbances may shed light on genotypic variations in liver disease progression and promotion of hepatocellular cancer in HCV-G3

Effects of minor Gaelic football match play on markers of muscle damage, delayed onset muscle soreness and muscle function

Purpose: This study examined the alterations in circulating creatine kinase (CK) levels, leukocyte trafficking, delayed onset muscle soreness (DOMS), muscle function in response to Gaelic football match-play in male adolescents. Methods: Participants (n=30, age 17.41 ± 0.78 yr, height 176.42 ± 7.13 cm, and mass 72.03 ± 6.49 kg) played a specially organised 15-a-side Gaelic Football game of 60 min duration. Blood samples were taken before the game, immediately post-game (Post), 12 h postgame (12 h), 36 h post game (36 h) and 60 h post game (60 h). Subjective muscle soreness, sprint performance and peak force were measured post, 12 h, 36 h and 60 h. Heart rate and movement patterns were continuously measured throughout the game using telemetry and GPS tracking, respectively. Heavy to severe impacts were classified as acceleration G-forces ³ 7 recorded via portable accelerometry. Results: Participants covered an average distance of 6.1 ± 1.1 km during match play. The majority (72%) of the distance involved walking and jogging and high speed and maximal activity accounted for 10% of the total distance. There was a total of 155 impacts ≥ 7 G-forces. C K levels were significantly higher than baseline immediately post-game and 12 h and returned to pregame values at 36 h. Compared to pre-match values circulating leukocytes and granulocytes were significantly higher than pre-game values immediately after the game and decreased significantly below pre-games values at 12h, 36 h and 60 h. Circulating lymphocyte numbers were significantly decreased below immediately post game and at 36 h post game. There was no change in the number of circulating monocytes. Compared to pre-game values, there was a significant decrease in peak force at 12 h and 60 h and a significant increase in 5 m and 20 m sprint times at 12 h, 36 h and 60 h. DOMS scores were significantly higher than pre-games values at 12 h and 36 h and lower (p<0.05) than pre-game values at 60 h. There was no significant relation between impacts and CK levels. Conclusion: Competitive Gaelic football match results in significant changes in CK levels, DOMS, leukocyte trafficking, peak force and 5 m and 20 m sprint performance

Depressive symptoms in chronic hepatitis C are associated with plasma apolipoprotein E deficiency

Neuro-psychiatric and cognitive disorders are frequent in patients with chronic hepatitis C (CHC) virus (HCV) infection which adversely impact quality of life, antiviral treatment adherence and outcome. HCV has neurotrophic properties and affects lipid metabolism, essential for cognitive function. We evaluated the relationship of lipid profiles with depression and anxiety symptoms and the effects of 12-weeks of therapy with fluvastatin and omega-3 ethyl esters (n-3 PUFA) in a randomised pilot study of CHC prior non-responders. Participants (n = 60) had fasting lipid profiles and assessment of depression and anxiety symptoms using the Hospital Anxiety and Depression Scale (HADS) questionnaire at each study visit. At screening 26/60 (43 \%) had HADS-A score a parts per thousand yen8 and 13/60 (22 \%) had HADS-D scores a parts per thousand yen8. Depressed patients had significantly lower apolipoprotein-E concentrations (30 mg/l vs 39 mg/l, P = 0.029) than those without depression and a tendency toward lower total cholesterol (3.8 vs 4.4 mmol/l, P = 0.053). 3 patients discontinued lipid-modifying treatment because of worsening depression. However, there was a small but significant improvement in anxiety symptoms after 12-weeks of high-dose (2-4 g daily) n-3 PUFA. In conclusion, depression in CHC is associated with plasma apoE deficiency. We postulate that apoE deficiency disrupts blood brain barrier integrity to promote HCV infection of the CNS. High-dose n-PUFAs may alleviate anxiety in some CHC patients but the use of lipid lowering therapy must be balanced against risks of worsening depression

Apolipoprotein-E and hepatitis C lipoviral particles in genotype 1 infection: Evidence for an association with interferon sensitivity

Background & Aims: Hepatitis C virus (HCV) interacts with apolipoproteins B (apoB) and E (apoE) to form infectious lipoviral particles (LVP). Response to peginterferon is influenced by interferon-stimulated genes (ISGs) and IL28B genotype. LDL cholesterol (LDL-C) also predicts interferon response, therefore we hypothesised that LVP may also be associated with interferon sensitivity. Methods: LVP (HCV RNA density 1.07 g/ml) were measured in 72 fasted HCV-G1 patients by iodixanol density gradient ultracentrifugation and the LVP ratio (LVP/LVP + non-LVP) was calculated. Fasting lipid profiles and apolipoproteins B and E were measured. Interferon-gamma-inducible protein 10 kDa (IP10), a marker of ISGs, was measured by ELISA. Results: Complete early virological response (EVR) was associated with lower apoE (23.9 +/- 7.7 vs. 36.1 +/- 15.3 mg/L, p = 0.013), higher LDL-C (p = 0.039) and lower LVP ratios (p = 0.022) compared to null responders. In multivariate linear regression analysis, apoE was independently associated with LVP (R-2 19.5%, p = 0.003) and LVP ratio (p = 0.042), and negatively with LDL-C (p < 0.001). IP10 was significantly associated with ApoB (p = 0.001) and liver stiffness (p = 0.032). IL28B rs12979860 CC was associated with complete EVR (p = 0.044), low apoE (CC 28 +/- 11 vs. CT/TT 35 +/- 13 mg/L, p = 0.048) and higher non-LVP (p = 0.008). Logistic regression analysis indicated that patients with high LVP ratios were less likely to have EVR (odds ratio 0.01, p = 0.018). Conclusions: In HCV-G1, interferon sensitivity is characterised by low LVP ratios and low apoE levels in addition to higher LDL-C and IL28B rs12979860 CC. Null-response is associated with increased LVP ratio. The association of apoE and LVP with peginterferon treatment response suggests that lipid modulation is a potential target to modify interferon sensitivit

Omega-3 fatty acids and/or fluvastatin in hepatitis C prior non-responders to combination anti-viral therapy - a pilot randomised clinical trial

Background & Aims Hepatitis C virus (HCV) utilises cholesterol and lipoprotein metabolism for replication and infectivity. Statins and omega-3 (n–3) polyunsaturated fatty acids (PUFA) have been shown to have antiviral properties in vitro. This open label pilot study evaluated the efficacy of fluvastatin (Lescol® 40–80 mg) and n-3 PUFA (Omacor®1 g and 2–4 g) on HCV-RNA and lipoviral particles (LVP) in difficult to treat prior non-responders. Methods Patients (n = 60) were randomly allocated in a factorial design to: no active drug; low-dose n-3 PUFA; high-dose n-3 PUFA; fluvastatin; low-dose n-3 PUFA + fluvastatin; or high-dose n-3 PUFA + fluvastatin. 50/60 completed study drugs for 12 weeks and followed up to week 24. Comparison was made between fluvastatin (n = 24) vs no fluvastatin (n = 26) and n-3 PUFA high-dose (n = 17) vs low-dose (n = 17) vs none (n = 16). The primary outcomes were change in total HCV-RNA, LVP and ALT at week 12 compared with baseline. Secondary outcome was change in interferon-gamma-inducible protein-10 (IP10) as a measure of interferon activation. Results 35% had compensated cirrhosis and 45% were prior null responders. There was no significant change in total HCV RNA, LVP, non-LVP or LVP ratio in patients receiving fluvastatin or n-3 PUFAs. ALT was not significantly different in those treated with fluvastatin or n-3 PUFAs. 12 weeks of low-dose n-3 PUFA decreased median IP10 concentration by −39 pg/ml (−111, 7.0 pg/ml Q1–Q3). Conclusions Fluvastatin and n-3 PUFAs have no effect on plasma HCV-RNA or LVP. The effect of low-dose n-3 PUFA on IP10 warrants further prospective evaluation as a supplemental therapy to enhance interferon sensitivity