Topologically-imposed vacancies and mobile solid 3He on carbon nanotube.

Low dimensional fermionic quantum systems are exceptionally interesting because they reveal distinctive physical phenomena, including among others, topologically protected excitations, edge states, frustration, and fractionalization. Our aim was to confine 3He on a suspended carbon nanotube to form 2-dimensional Fermi-system. Here we report our measurements of the mechanical resonance of the nanotube with adsorbed sub-monolayer down to 10 mK. At intermediate coverages we have observed the famous 1/3 commensurate solid. However, at larger monolayer densities we have observed a quantum phase transition from 1/3 solid to an unknown, soft, and mobile solid phase. We interpret this mobile solid phase as a bosonic commensurate crystal consisting of helium dimers with topologically-induced zero-point vacancies which are delocalized at low temperatures. We thus demonstrate that 3He on a nanotube merges both fermionic and bosonic phenomena, with a quantum phase transition between fermionic solid 1/3 phase and the observed bosonic dimer solid.

Mid-term functional and quality of life outcomes of robotic and laparoscopic ventral mesh rectopexy: multicenter comparative matched-pair analyses.

BACKGROUND: The aim of this study was to compare patients' mid-term functional and quality of life (QoL) outcomes following robotic ventral mesh rectopexy (RVMR) and laparoscopic ventral mesh rectopexy (LVMR). METHODS: The data of consecutive female patients who underwent minimally invasive ventral mesh rectopexy for external or symptomatic internal rectal prolapse at 3 hospitals in Finland between January 2011 and December 2016 were retrospectively collected. Patients were matched by age and diagnosis at a 1:1 ratio. A disease-related symptom questionnaire was sent to all living patients at follow-up in July 2018. RESULTS: After a total of 401 patients (RVMR, n = 187; LVMR, n = 214) were matched, 152 patients in each group were included in the final analyses. The median follow-up times were 3.3 (range 1.6-7.4) years and 3.0 (range 1.6-7.6) years for the RVMR and LVMR groups, respectively. The postoperative QoL measures did not differ between the groups. Compared with the LVMR group, the RVMR group had lower postoperative Wexner Incontinence Score (median 5 vs. median 8; p < 0.001), experienced significant ongoing incontinence symptoms less often (30.6% vs. 49.0%; p < 0.001) and reported less postoperative faecal incontinence discomfort evaluated with the visual analogue scale (median 11 vs. median 39; p = 0.005). RVMR patients had a shorter hospital stay (2.2 days vs. 3.8 days; p < 0.001) but experienced more frequent de novo pelvic pain (31.8% vs. 11.8%; p < 0.001). CONCLUSION: RVMR and LVMR patients had equal functional and QoL outcomes. Those who underwent RVMR had lower mid-term anal incontinence symptom scores but suffered more frequent de novo pelvic pain.

Redo ventral rectopexy: is it worthwhile?

BACKGROUND: Minimally invasive ventral mesh rectopexy (VMR) is a widely used surgical treatment for posterior pelvic organ prolapse; however, evidence of the utility of revisional surgery is lacking. Our aim was to assess the technical details, safety and outcomes of redo minimally invasive VMR for patients with external rectal prolapse (ERP) recurrence or relapsed symptoms of internal rectal prolapse (IRP). METHODS: This is a retrospective cohort study of patients with recurrent ERP or symptomatic IRP who underwent redo minimally invasive VMR between 2011 and 2016. The study was conducted at three hospitals in Finland. Data collected retrospectively included patient demographics, in addition to perioperative and short-term postoperative findings. At follow-up, all living patients were sent a questionnaire concerning postoperative disease-related symptoms and quality of life. RESULTS: A total of 43 redo minimally invasive VMR were performed during the study period. The indication for reoperation was recurrent ERP in 22 patients and relapsed symptoms of IRP in 21 patients. In most operations (62.8%), the previously used mesh was left in situ and a new one was placed. Ten (23.3%) patients experienced complications, including 2 (4.7%) mesh-related complications. The recurrence rate was 4.5% for ERP. Three patients out of 43 were reoperated on for various reasons. One patient required postoperative laparoscopic hematoma evacuation. Patients operated on for recurrent ERP seemed to benefit more from the reoperation. CONCLUSIONS: Minimally invasive redo VMR appears to be a safe and effective procedure for treating posterior pelvic floor dysfunction with acceptable recurrence and reoperation rates.

Restored pelvic anatomy is preserved after laparoscopic and robot-assisted ventral rectopexy: MRI-based 5-year follow-up of a randomized controlled trial.

AIM: Our aim was to compare the long-term anatomical outcomes between robot-assisted ventral mesh rectopexy (RVMR) and laparoscopic ventral mesh rectopexy (LVMR) for external or internal rectal prolapse. METHOD: This study is a follow-up of a single-centre randomized controlled trial (RCT). Thirty patients were randomly allocated to RVMR (n = 16) or LVMR (n = 14). The primary end-point was maintenance of the restored pelvic anatomy 5 years after the operation, as assessed by magnetic resonance (MR) defaecography. Secondary outcome measures included the Pelvic Organ Prolapse Quantification (POP-Q) measures and functional results assessed using symptom questionnaires. RESULTS: Twenty-six patients (14 RVMR and 12 LVMR) completed the 5-year follow-up and were included in the study. The MRI results, POP-Q measurements and symptom-specific quality of life measures did not differ between the RVMR and LVMR groups. The MRI measurements of the total study population remained unchanged between 3 months and 5 years. In the Pelvic Floor Distress Inventory (PFDI-20), the RVMR group had lower symptom scores (mean 96.0, SD 70.7) than the LVMR group (mean 160.6, SD 58.9; P = 0.004). In the subscales of pelvic organ prolapse (POPDI-6) (mean 23.2, SD 24.3 vs mean 52.4, SD 22.4; P = 0.001) and the Colorectal-Anal Distress Inventory (CRADI-8) (mean 38.4, SD 23.3 vs mean 58.6, SD 25.4; P = 0.009), the patients in the RVMR group had significantly better outcomes. CONCLUSION: After VMR, the corrected anatomy was preserved. There were no clinically significant differences in anatomical results between the RVMR and LVMR procedures 5 years after surgery based on MR defaecography. However, functional outcomes were better after RMVR.

A prospective pilot study on MRI visibility of iron oxide-impregnated polyvinylidene fluoride mesh after ventral rectopexy.

BACKGROUND: Magnetic resonance imaging (MRI) provides excellent information about pelvic anatomy after ventral rectopexy, but the position of the conventional mesh is not seen constantly. Iron oxide-impregnated polyvinylidene fluoride (PVDF) meshes are proven to have MRI visibility in hernia or vaginal reconstructive surgery. This prospective pilot study was designed to assess the visualization, position, and shape of the magnetic resonance (MR)-visible synthetic pelvic mesh used in minimally invasive ventral rectopexy. METHODS: Eight patients with pelvic organ prolapse were recruited for laparoscopic (LVMR) or robotic-assisted ventral mesh rectopexy (RVMR) with a synthetic MR-visible PVDF mesh. A follow-up visit was scheduled at 3 months after surgery. MR imaging was performed to evaluate the position and dimensions of the mesh and anatomical result. The visibility of the mesh in each sequence was assessed subjectively. RESULTS: The visibility of the mesh was best on T1-weighted flash images. The mesh was also well visualized on T2-weighted sagittal images. T2-weighted images, in general, provided best visualization of the surrounding anatomical structures and enabled assessment of the mesh fixation. CONCLUSIONS: T2 sagittal and T1-weighted flash images provide the best information about the position and integrity of the iron oxide-impregnated PVDF mesh after LVMR or RVMR with a short examination time.

Cost-analysis and quality of life after laparoscopic and robotic ventral mesh rectopexy for posterior compartment prolapse: a randomized trial.

BACKGROUND: The aim of this study was to assess, whether robotic-assistance in ventral mesh rectopexy adds benefit to laparoscopy in terms of health-related quality of life (HRQoL), cost-effectiveness and anatomical and functional outcome. METHODS: A prospective randomized study was conducted on patients who underwent robot-assisted ventral mesh rectopexy (RVMR) or laparoscopic ventral mesh rectopexy (LVMR) for internal or external rectal prolapse at Oulu University Hospital, Finland, recruited in February-May 2012. The primary outcomes were health care costs from the hospital perspective and HRQoL measured by the 15D-instrument. Secondary outcomes included anatomical outcome assessed by pelvic organ prolapse quantification method and functional outcome by symptom questionnaires at 24 months follow-up. RESULTS: There were 30 females (mean age 62.5 years, SD 11.2), 16 in the RVMR group and 14 in the LVMR group. The surgery-related costs of the RVMR were 1.5 times higher than the cost of the LVMR. At 3 months the changes in HRQoL were 'much better' (RVMR) and 'slightly better' (LVMR) but declined in both groups at 2 years (RVMR vs. LVMR, p > 0.05). The cost-effectiveness was poor at 2 years for both techniques, but if the outcomes were assumed to last for 5 years, it improved significantly. The incremental cost-effectiveness ratio for the RVMR compared to LVMR was €39,982/quality-adjusted life years (QALYs) at 2 years and improved to €16,707/QALYs at 5 years. Posterior wall anatomy was restored similarly in both groups. The subjective satisfaction rate was 87% in the RVMR group and 69% in the LVMR group (p = 0.83). CONCLUSIONS: Although more expensive than LVMR in the short term, RVMR is cost-effective in long-term. The minimally invasive VMR improves pelvic floor function, sexual function and restores posterior compartment anatomy. The effect on HRQoL is minor, with no differences between techniques.

Laparoscopic ventral rectopexy in male patients with external rectal prolapse is associated with a high reoperation rate.

BACKGROUND: Laparoscopic ventral rectopexy has been used to treat male patients with external rectal prolapse, but evidence to support this approach is scarce. The aim of this study was to evaluate the results of this new abdominal rectopexy surgical technique in men. METHODS: This was a retrospective multicenter study. Adult male patients who were operated on for external rectal prolapse using ventral rectopexy in five tertiary hospitals in Finland between 2006 and 2014 were included in the study. Patient demographics, detailed operative, postoperative and short-term follow-up data were collected from patient registers in participating hospitals. A questionnaire and informed consent form was sent to all patients. The questionnaire included scores for anal incontinence, obstructed defecation syndrome, urinary symptoms and sexual dysfunction. The main outcome measure was the incidence of recurrent rectal prolapse. Surgical morbidity, the need for surgical repair due to recurrent symptoms and functional outcomes were secondary outcome measures. RESULTS: A total of 52 adult male patients with symptoms caused by external rectal prolapse underwent ventral rectopexy. The questionnaire response rate was 64.4 %. Baseline clinical characteristics and perioperative results were similar in the responder and non-responder groups. A total of 9 (17.3 %) patients faced complications. There were two (3.8 %) serious surgical complications during the 30-day period after surgery that necessitated reoperation. None of the complications were mesh related. Recurrence of the prolapse was noticed in nine patients (17 %), and postoperative mucosal anal prolapse symptoms persisted in 11 patients (21 %). As a result, the reoperation rate was high. Altogether, 17 patients (33 %) underwent reoperation during the follow-up period due to postoperative complications or recurrent rectal or mucosal prolapse. According to the postoperative questionnaire data, patients under 40 had good functional results in terms of anal continence, defecation, urinary functions and sexual activity. CONCLUSIONS: Laparoscopic ventral rectopexy is a safe surgical procedure in male patients with external prolapse. However, a high overall reoperation rate was noticed due to recurrent rectal and residual mucosal prolapse. This suggests that the ventral rectopexy technique should be modified or combined with other abdominal or perineal methods when treating male rectal prolapse patients.

Robot-assisted vs laparoscopic ventral rectopexy for external or internal rectal prolapse and enterocele: a randomized controlled trial.

AIM: The purpose of this prospective randomized study was to compare robot-assisted and laparoscopic ventral rectopexy procedures for posterior compartment procidentia in terms of restoration of the anatomy using magnetic resonance (MR) defaecography. METHOD: Sixteen female patients (four with total prolapse, twelve with intussusception) underwent robot-assisted ventral mesh rectopexy (RVMR) and 14 female patients (two with prolapse, twelve with intussusception) laparoscopic ventral mesh rectopexy (LVMR). Primary outcome measures were perioperative parameters, complications and restoration of anatomy as assessed by MR defaecography, which was performed preoperatively and 3 months after surgery. RESULTS: Patient demographics, operation length, operating theatre times and length of in-hospital stay were similar between the groups. The anatomical defects of rectal prolapse, intussusception and rectocele and enterocele were similarly corrected after rectopexy in either technique as confirmed with dynamic MR defaecography. A slight residual intussusception was observed in three patients with primary total prolapse (two RVMR vs one LVMR) and in one patient with primary intussusception (RVMR) (P = 0.60). Rectocele was reduced from a mean of 33.0 ± 14.9 mm to 5.5 ± 8.4 mm after RVMR (P < 0.001) and from 24.7 ± 17.5 mm to 7.2 ± 3.2 mm after LVMR (P < 0.001) (RVMR vs LVMR, P = 0.10). CONCLUSION: Robot-assisted laparoscopic ventral rectopexy can be performed safely and within the same operative time as conventional laparoscopy. Minimally invasive ventral rectopexy allows good anatomical correction as assessed by MR defaecography, with no differences between the techniques.

Dry demagnetization cryostat for sub-millikelvin helium experiments: refrigeration and thermometry.

We demonstrate successful "dry" refrigeration of quantum fluids down to T = 0.16 mK by using copper nuclear demagnetization stage that is pre-cooled by a pulse-tube-based dilution refrigerator. This type of refrigeration delivers a flexible and simple sub-mK solution to a variety of needs including experiments with superfluid (3)He. Our central design principle was to eliminate relative vibrations between the high-field magnet and the nuclear refrigeration stage, which resulted in the minimum heat leak of Q = 4.4 nW obtained in field of 35 mT. For thermometry, we employed a quartz tuning fork immersed into liquid (3)He. We show that the fork oscillator can be considered as self-calibrating in superfluid (3)He at the crossover point from hydrodynamic into ballistic quasiparticle regime.

High serum n6 fatty acid proportion is associated with lowered LDL oxidation and inflammation: the Cardiovascular Risk in Young Finns Study.

The intake of polyunsaturated fatty acids (PUFAs) is generally linked with a reduced cardiovascular disease (CVD) risk, but an elevated n6PUFA intake, without simultaneous n3PUFA supply, may elevate the risk. PUFAs are suspected as being easily oxidized and have a potential role in lipoprotein oxidation and inflammation. Saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs) are resistant to oxidation. However, in a Western diet, their most important source is red meat, a food stuff rich in heme iron which can catalyze oxidative reactions. Therefore, different serum fatty acid (FA) proportions (free + esterified) were correlated with the status of low-density lipoprotein (LDL) oxidation in vivo (conjugated dienes = oxLDLlipids and antibody-based oxidized proteins = oxLDLprot) and inflammation (serum CRP) in 2196 Finnish subjects (age: 24-39 years) using CVD risk factor-adjusted linear regression models. High n6PUFA, PUFA/SFA and n6/n3 ratios, and low SFA and MUFA were all associated with reduced levels of oxLDLlipids, oxLDLprot, and CRP. These findings at the population level suggest that PUFAs are negatively and SFAs and MUFAs positively related with LDL oxidation and inflammation; these conclusions are in line with previous observations linking PUFAs, particularly n6PUFAs, with lower CVD risk, and SFAs with increased risk.

Robotic-assisted and laparoscopic ventral rectopexy in the treatment of rectal prolapse: a matched-pairs study of operative details and complications.

BACKGROUND: Laparoscopic ventral rectopexy has been proven to be safe and effective in the treatment of rectal prolapse or intussusception. Robotic-assisted surgery may offer potential benefits to this operation. This study describes the comparison of robotic-assisted and conventional laparoscopic ventral rectopexy in terms of clinical parameters, operative details, postoperative complications and short-term outcomes. METHODS: Twenty patients operated on for rectal prolapse or intussusception using the Da Vinci Surgical System (Intuitive Surgical Inc, Sunnyvale CA, USA) were prospectively followed for 3 months. The cases were pair-matched with laparoscopically operated controls from registry files. RESULTS: Mean operating time was 159 min (standard deviation; ±37 SD) and 153 min (±33 SD) and mean total time in the operating theatre 231 min (±39 SD) and 234 min (±41 SD) for robotic-assisted and laparoscopic operations, respectively. Mean blood loss was 25 ml (±49 SD) in robotic-assisted and 37 ml (±50 SD) in laparoscopic procedures. There was one (5 %) significant complication in each group. Mean length of hospital stay was 3.1 (±2 SD) and 3.3 (±1.3 SD) days for the robotic-assisted and laparoscopic groups, respectively. The subjective benefit rate was the same in both groups: 16/20 (80 %). One patient in the robotic-assisted group continued to have symptoms of obstructed defecation, and there was one recurrence of prolapse in the laparoscopic group. CONCLUSIONS: Robotic-assisted laparoscopic ventral rectopexy is safe, feasible and not more time consuming than the laparoscopic technique even at the beginning of the learning curve. The short-term results are comparable with those of laparoscopy. We found no arguments to support the routine use of robotic assistance in rectopexy operations.

Cardiovascular risk factors in type 2 diabetic patients in Bulgaria.

UNLABELLED: Type 2 diabetes mellitus is associated with an excessively high morbidity and mortality from cardiovascular disease. Macrovascular disease with its complications is the leading cause of death in Bulgaria. AIM OF THIS STUDY: To examine cardiovascular risk factors in patients with type 2 diabetes. MATERIAL AND METHODS: The study included 556 patients with type 2 diabetes and 575 healthy subjects. All participants filled a questionnaire on medical history, lifestyle and family history and standardised measurements were taken of some of their anthropometric parameters and blood pressure. Venous blood was drawn after an overnight fast for the examination of glucose, lipids, C-reactive protein and other cardiovascular risk factors. RESULTS: Seventy-eight percent of the diabetic subjects had a history of coronary heart disease. The diabetics had significantly higher body mass index (27.1 +/- 4.4 kg/m2 vs. 25.0 +/- 3.8 kg/m2; mean +/- SD), waist circumference (101 +/- 10.2 vs. 87 +/- 8), systolic (131 +/- 12 mm Hg vs. 123 +/- 11) and diastolic blood pressure (85 +/- 9 mm Hg vs. 78 +/- 7), blood glucose (8.4 +/- 2.3 mmol/l vs. 5.4 +/- 0.7), total cholesterol (5.8 +/- 0.78 mmol/l vs. 4.9 +/- 1.0), triglycerides (2.18 +/- 1.02 mmol/l vs. 0.98 +/- 0.60) and C-reactive protein (5.2 +/- 3.9 vs. 3.7 +/- 3.1 mg/l) as well as significantly lower levels of HDL-cholesterol (0.96 +/- 0.28 mmol/l vs. 1.45 +/- 0.47) vs. controls. CONCLUSIONS: Our study demonstrates that patients with type 2 diabetes in Bulgaria have significantly increased levels of cardiovascular risk factors, which could explain the excessive cardiovascular mortality of these patients.

C18 hydroxy fatty acids as markers of lipid peroxidation ex vivo and in vivo.

Different C18 monohydroxy fatty acids (OHFAs) were evaluated for their usefulness as markers of plasma lipid peroxidation (unsaturated fatty acid oxidation) ex vivo and in vivo. First, plasma samples (n = 5) were exposed for 3 h to different radical fluxes ex vivo. The formation of OHFAs was assessed by using varying concentrations of Cu2+ ions and AAPH (2,2'-azobis(2-amidinopropane) hydrochloride) as radical flux initiators. Secondly, a cross-sectional study was carried out in 47 middle-aged men. In this study, plasma concentrations of different in vivo OHFAs were compared with other indices of lipid peroxidation. Under mild oxidation conditions (heparin plasma containing 4.2 or 8.3 mM AAPH), concentrations of all the measured OHFAs (8, 9, 10, 11, 12, 13, 15 and 16-OH acids) increased in an identical manner, but under highly oxidative conditions (heparin plasma containing 83 mM AAPH or 4.2 to 8.3 mM CuSO4) mainly 9 and 13-OHFAs were formed. In the cross-sectional study, plasma 11 and 13-OHFA levels were associated statistically significantly with plasma free F2alpha-isoprostanes, recognized index of in vivo lipid peroxidation (r = 0.305, p = 0.037 and r = 0.308, p = 0.035, respectively). In addition, 16-OHFA levels correlated with the ratio of electronegatively charged LDL to total LDL (r = 0.335, p = 0.021). With respect to the other OHFAs, 15-OHFA had no correlation with either other OHFAs or the reference substances used. In addition, occasionally there were contamination problems in the assessment of 12-OHFA. It is concluded that all of the measured C18 OHFAs can be used as indicators of plasma lipid peroxidation under mild oxidation conditions, though the 12 and 15-OHFAs may need to be used with some caution. Under high oxidation conditions, 9-and 13-OHFAs seem to be the most useful indices because of their high formation capacity.

Exhaustive exercise increases plasma/serum total oxidation resistance in moderately trained men and women, whereas their VLDL + LDL lipoprotein fraction is more susceptible to oxidation.

The purpose of this study was to evaluate the effects of exhaustive exercise (marathon run) on different lipid peroxidation measurements, including copper-induced serum lipids and VLDL + LDL oxidation susceptibility, and on plasma total antioxidative capacity (TRAP), muscular damage and plasma antioxidants in healthy moderately trained male (n = 21) and female (n = 25) volunteers. Blood samples were taken before and just after the 42-km run. In women, baseline levels of several antioxidative compounds (serum albumin and uric acid, plasma free thiols and blood glutathione) were lower, resulting in 21.5% lower plasma total antioxidative capacity and 70.3% higher serum oxidation susceptibility, compared to men. To compare effects in men and women, the exercise-induced variable changes were adjusted for their baseline levels. After this adjustment, there were no statistically significant differences between the genders in the extent of muscular damage (serum creatine kinase, (CK)), or in the change in serum lipids or VLDL + LDL oxidation susceptibility, or that of plasma antioxidative capacity. A possible beneficial effect of exercise was that serum HDL cholesterol levels increased significantly in both genders, but especially in women. In the group of pooled genders (n=46), the increases in serum CK and in plasma lactate were 190% (95% CI, 133% to 246%) and 109% (95% CI, 65% to 175%), respectively. On the basis of our lipid peroxidation and TRAP measurements, uric acid was observed to be the most important plasma antioxidant. The effect of exercise was to decrease the oxidation susceptibility of serum lipids by 24.8% (95% CI 13.4% to 36.2%) and to elevate plasma TRAP by 14.6% (95% CI, 11.4% to 17.7%). Nonetheless, the oxidation susceptibility of the VLDL + LDL fraction increased by 11.0% (95% CI, 1.9% to 20.2%). Our results suggest that there are no gender-based differences in exhaustive exercise-induced lipid peroxidation or muscular damage. Secondly, even though exhaustive exercise can increase plasma/serum total resistance towards oxidation, the oxidation resistance of the atherogenic lipoprotein fraction might be diminished. On the basis of these results, several in vitro measurements of lipid peroxidation assessing both water and lipid soluble plasma fractions are needed if a true perspective of the plasma redox status is to be obtained.

Supplementation with vitamin E but not with vitamin C lowers lipid peroxidation in vivo in mildly hypercholesterolemic men.

Although the use of vitamin E supplements has been associated with a reduction in coronary events, assumed to be due to lowered lipid peroxidation, there are no previous long-term clinical trials into the effects of vitamin C or E supplementation on lipid peroxidation in vivo. Here, we have studied the long-term effects of vitamins C and E on plasma F2-isoprostanes, a widely used marker of lipid peroxidation in vivo. As a study cohort, a subset of the "Antioxidant Supplementation in Atherosclerosis Prevention" (ASAP) study was used. ASAP is a double-masked placebo-controlled randomized clinical trial to study the long-term effect of vitamin C (500 mg of slow release ascorbate daily), vitamin E (200 mg of D-alpha-tocopheryl acetate daily), both vitamins (CellaVie), or placebo on lipid peroxidation, atherosclerotic progression, blood pressure and myocardial infarction (n = 520 at baseline). Lipid peroxidation measurements were carried out in 100 consecutive men at entry and repeated at 12 months. The plasma F2-isoprostane concentration was lowered by 17.3% (95% CI 3.9-30.8%) in the vitamin E group (p = 0.006 for the change, as compared with the placebo group). On the contrary, vitamin C had no significant effect on plasma F2-isoprostanes as compared with the placebo group. There was also no interaction in the effect between these vitamins. In conclusion, long-term oral supplementation of clinically healthy, but hypercholesterolemic men, who have normal vitamin C and E levels with a reasonable dose of vitamin E lowers lipid peroxidation in vivo, but a relatively high dose of vitamin C does not. This observation may provide a mechanism for the observed ability of vitamin E supplements to prevent atherosclerosis.

Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) study: a randomized trial of the effect of vitamins E and C on 3-year progression of carotid atherosclerosis.

OBJECTIVES: To study the efficacy of vitamin E and C supplementation on the progression of carotid atherosclerosis, hypothesizing an enhanced preventive effect in men and in smokers and synergism between vitamins. DESIGN AND SUBJECTS: Double-masked two-by-two factorial trial, randomization in four strata (by gender and smoking status) to receive twice daily either 91 mg (136 IU) of d-alpha-tocopherol, 250 mg of slow-release vitamin C, a combination of these or placebo for three years. A randomized sample of 520 smoking and nonsmoking men and postmenopausal women aged 45-69 years with serum cholesterol >/= 5.0 mmol L-1 were studied. SETTING: The population of the city of Kuopio in Eastern Finland. INTERVENTION: Twice daily either a special formulation of 91 mg of d-alpha-tocopherol, 250 mg of slow-release vitamin C, a combination of these (CellaVie(R)) or placebo for three years. MEASUREMENTS: Atherosclerotic progression, defined as the linear regression slope of ultrasonographically assessed common carotid artery mean intima-media thickness (IMT), was calculated over semi-annual assessments. RESULTS: The average increase of the mean IMT was 0.020 mm year-1 amongst men randomized to placebo and 0.018 mm year-1 in vitamin E, 0.017 mm year-1 in vitamin C and 0.011 mm year-1 in the vitamin combination group (P = 0.008 for E + C vs. placebo). The respective means in women were 0.016, 0.015, 0.017 and 0.016 mm year-1. The proportion of men with progression was reduced by 74% (95% CI 36-89%, P = 0.003) by supplementation with the formulation containing both vitamins, as compared with placebo. CONCLUSIONS: Our study shows that a combined supplementation with reasonable doses of both vitamin E and slow-release vitamin C can retard the progression of common carotid atherosclerosis in men. This may imply benefits with regard to other atherosclerosis-based events.

Long-term effects of vitamin E, vitamin C, and combined supplementation on urinary 7-hydro-8-oxo-2'-deoxyguanosine, serum cholesterol oxidation products, and oxidation resistance of lipids in nondepleted men.

We studied the long-term effects of vitamins E and C and their combination on lipid peroxidation in vivo and in vitro. The Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) trial is a double-masked placebo-controlled randomized clinical trial to study the effects of vitamin C (500 mg of slow release ascorbate per day), vitamin E (182 mg of RRR-alpha-tocopherol acetate per day), and the combination of both antioxidants. Lipid peroxidation measurements were carried out for 48 male participants at entry and at 12 and 36 months. Compared with placebo, vitamin E and the vitamin combination increased plasma lipid-standardized alpha-tocopherol during the first 12 months by 68.2% and 65.2% (P:<0. 001 for both), respectively, and reduced serum 7beta-hydroxycholesterol by 50.4% (P:=0.013) and 44.0% (P:=0.041), respectively. The net change of lipid standardized alpha-tocopherol was 63.8% after 36 months of vitamin E supplementation and 43.3% for the combination. Vitamin C supplementation elevated plasma total ascorbate level by 30.1% (P:=0.043) in 12 months and by 91.1% (P:=0. 001) in 36 months. Neither vitamin E, vitamin C, nor the combination influenced the urinary excretion rate of 7-hydro-8-oxo-2'-deoxyguanosine or the antioxidative capacity of plasma. Vitamin E and the combination of vitamins E and C enhanced the oxidation resistance of isolated lipoproteins and total serum lipids. Our data indicate that long-term supplementation of nondepleted men with a reasonable dose of vitamin E alone or in combination with slow release vitamin C reduces lipid peroxidation in vitro and in vivo, whereas a relatively high dose of vitamin C alone does not.

Antioxidative efficacy of parallel and combined supplementation with coenzyme Q10 and d-alpha-tocopherol in mildly hypercholesterolemic subjects: a randomized placebo-controlled clinical study.

It has been claimed that coenzyme Q10 (Q10) would be an effective plasma antioxidant since it can regenerate plasma vitamin E. To test separate effects and interaction between Q10 and vitamin E in the change of plasma concentrations and in the antioxidative efficiency, we carried out a double-masked, double-blind clinical trial in 40 subjects with mild hypercholesterolemia undergoing statin treatment. Subjects were randomly allocated to parallel groups to receive either Q10 (200 mg daily), d-alpha-tocopherol (700 mg daily), both antioxidants or placebo for 3 months. In addition we investigated the pharmacokinetics of Q10 in a separate one-week substudy. In the group that received both antioxidants, the increase in plasma Q10 concentration was attenuated. Only vitamin E supplementation increased significantly the oxidation resistance of isolated LDL. Simultaneous Q10 supplementation did not increase this antioxidative effect of vitamin E. Q10 supplementation increased and vitamin E decreased significantly the proportion of ubiquinol of total Q10, an indication of plasma redox status in vivo. The supplementations used did not affect the redox status of plasma ascorbic acid. In conclusion, only vitamin E has antioxidative efficiency at high radical flux ex vivo. Attenuation of the proportion of plasma ubiquinol of total Q10 in the vitamin E group may represent in vivo evidence of the Q10-based regeneration of the tocopheryl radicals. In addition, Q10 might attenuate plasma lipid peroxidation in vivo, since there was an increased proportion of plasma ubiquinol of total Q10.

Measurement and stability of plasma reduced, oxidized and total coenzyme Q10 in humans.

There are findings indicating that a decreased ratio of plasma coenzyme Q10 (Q10) to LDL cholesterol could be associated with an increased risk of atherosclerosis. Furthermore, the proportion of plasma Q10H2 (reduced Q10, ubiquinol) of total Q10 has been shown to be attenuated in major diseases, such as hyperlipidemia and coronary artery disease. These observations suggest that measurement of plasma total Q10 and the proportion of plasma Q10H2 of total Q10 would be of clinical significance. However, epidemiological studies addressing this issue require large numbers of subjects, and measurements from unfrozen samples are unfeasible. For this reason, we evaluated the stability of Q10 samples during sample storage and processing. We also compared solid phase and hexane pre-treatments prior to high-performance liquid chromatographic determination of Q10. Our results indicate that samples for plasma total Q10 measurement can be pre-treated in normal laboratory lighting conditions, thawed and frozen several times, and stored deep frozen for a couple of years without changes in measured Q10 values. If purification of the samples by silica and C18 is needed, the best reproducibility tends to be achieved with powder treatment (not with cartridges). However, to measure successfully the proportion of plasma ubiquinol of total Q10, samples must be thawed, extracted, and analysed one at a time and quickly to ensure minimal ubiquinol oxidation during the measurement process.

Determinants of plasma coenzyme Q10 in humans.

In the present study, we assessed the strongest determinants of plasma coenzyme Q10 (Qm10) in 518 men and women (aged 45-70 years) with a stepwise multivariate regression model. Male gender (P<0.001), serum cholesterol (P<0.001), serum gamma-glutamyltransferase (P<0.001), serum triglycerides (P< 0.001), age (P=0.017) and 4-day alcohol consumption (P=0.03) were the most important factors which were directly associated with plasma Q10). The intensity of conditioning exercise (P=0.03) and use of statins (P<0.05) showed an inverse association with plasma Q10. None of the assessed nutrients increased plasma Q10 levels significantly. Our results suggest that many confounding factors, in addition to serum cholesterol and triglycerides, should be taken into account when the role of plasma Q10 is examined in epidemiological research.