Insulin decreases plasma cholesteryl ester transfer but not cholesterol esterification in healthy subjects as well as in normotriglyceridaemic patients with type 2 diabetes

Background. Plasma cholesterol esterification (EST) and subsequent cholesteryl ester transfer (CET) from high-density lipoproteins (HDLs) towards apolipoprotein (apo) B-containing lipoproteins are key steps in HDL metabolism. Materials and methods. The effects of exogenous hyperinsulinaemia on plasma CET and EST, measured with isotope methods, were evaluated in 10 male normotriglyceridaemic (plasma triglycerides < 2.0 mmol L-1) patients with type 2 diabetes and 10 individually matched healthy subjects during a two-step hyperinsulinaemic euglycaemic clamp over 6-7 h. Results. No between-group differences in baseline plasma lipid parameters were observed, but the HDL cholesteryl ester content was lower (P < 0.02) and the HDL triglyceride content was higher (P < 0.05) in diabetic patients. Baseline CET and EST were similar in the groups. In both groups, hyperinsulinaemia decreased plasma triglycerides (P < 0.01) and the HDL triglyceride content (P < 0.01) compared with saline infusion in healthy subjects, whereas the HDL cholesteryl ester content increased (P < 0.05 vs. saline infusion) in diabetic patients. CET was similarly decreased by hyperinsulinaemia in both groups (P < 0.01 vs. saline infusion). In contrast, the change in EST in either group was not different from that during saline administration. In the combined group, baseline CET was positively correlated with plasma triglycerides (R(s) = 0.68, P < 0.01). The HDL cholesteryl ester content was negatively (R(s) = -0.48, P < 0.05) and the HDL triglyceride content was positively (R(s) = 0.64, P < 0.01) correlated with CET. Conclusion. Insulin infusion decreases plasma CET in conjunction with a fall in triglycerides but does not decrease cholesterol esterification in healthy and type 2 diabetic subjects, indicating that acute hyperinsulinaemia has a different effect on these processes involved in HDL metabolism. Despite unaltered fasting plasma CET, HDL core lipid composition was abnormal in diabetic patients, suggesting-that additional mechanisms may contribute to changes in HDL metabolism in diabetes mellitus

A Dutch translation of the Self-Efficacy for Rehabilitation Outcome Scale (SER):a first impression on reliability and validity

Self-efficacy is a relevant factor during rehabilitation after total hip or knee arthroplasty. Research was done into the reliability and validity of a Dutch translation of the Self-Efficacy for Rehabilitation Outcome Scale (SER). One hundred and forty-one persons filled in the SER questionnaire and the Self-Efficacy Expectation Scale (SES) as a control scale. Research was done into reliability and into construct- and criterion-related validity. Factor analysis yielded two factors. Pearson's correlation between the two factors was 0.61 (P <0.01). To assess criterion-related validity, the Pearson's correlation coefficient was calculated between the sum score of the SER and the SES. The scales had a correlation of 0.62 (P <0.01). Internal consistency resulted in a Cronbach's coefficient alpha of 0.94 for the entire SER scale, and 0.94 and 0.87 for the first and second factors. It is concluded that for the time being the Dutch version of the SER can be considered a reliable and valid questionnaire. (c) 2004 Elsevier Ireland Ltd. All rights reserved

The cholesterol-raising diterpenes from coffee beans increase serum lipid transfer protein activity levels in humans

Cafestol and kahweol–diterpenes present in unfiltered coffee— strongly raise serum VLDL and LDL cholesterol and slightly reduce HDL cholesterol in humans. The mechanism of action is unknown. We determined whether the coffee diterpenes may affect lipoprotein metabolism via effects on lipid transfer proteins and lecithin:cholesterol acyltransferase in a randomized, double-blind cross-over study with 10 healthy male volunteers. Either cafestol (61–64 mg/day) or a mixture of cafestol (60 mg/day) and kahweol (48–54 mg/day) was given for 28 days. Serum activity levels of cholesterylester transfer protein, phospholipid transfer protein and lecithin:cholesterol acyltransferase were measured using exogenous substrate assays. Relative to baseline values, cafestol raised the mean (±S.D.) activity of cholesterylester transfer protein by 18±12% and of phospholipid transfer protein by 21±14% (both P<0.001). Relative to cafestol alone, kahweol had no significant additional effects. Lecithin:cholesterol acyltransferase activity was reduced by 11±12% by cafestol plus kahweol (P=0.02). It is concluded that the effects of coffee diterpenes on plasma lipoproteins may be connected with changes in serum activity levels of lipid transfer proteins

Dietary trans fatty acids increase serum cholesterylester transfer protein activity in man

The average diet may provide some 8–10 g/day of unsaturated fatty acids with a trans double bond. Previous studies showed that dietary trans fatty acids may simultaneously raise low-density lipoprotein (LDL) cholesterol and reduce high-density lipoprotein (HDL) cholesterol. Human plasma contains a protein (CETP) which transfers cholesterylesters from HDL to lipoproteins of lower density. We hypothesized that CETP could play a role in the effect of trans fatty acids on lipoproteins and measured the activity levels of CETP in serum samples from a 9-week study in which 55 volunteers were fed three controlled diets with different fatty acid profiles. Mean activity was 114 (% of reference serum) after consumption of a high trans fatty acid diet, as opposed to 96 after linoleic acid and 97 after stearic acid (P < 0.02). We conclude that the increased activity of CETP may contribute to the rise in LDL cholesterol and the fall in HDL cholesterol seen on diets with high contents of trans fatty acids

Dialysis of isolated low density lipoprotein induces a loss of lipophilic antioxidants and increases the susceptibility to oxidation in vitro

We determined the effects of different dialysis conditions on the antioxidant content, duration of the lag phase and oxidation rate of LDL. Dialysis for 22 h resulted in a 56%–66% reduction in the concentrations of β-carotene, lycopene and α-tocopherol. The lag phase of copper-induced oxidation of freshly isolated LDL was considerably longer than that of LDL dialysed for 22 or 44 h. Our data show that dialysis may result in LDL preparations with antioxidant compositions that are not truly representative of freshly isolated lipoproteins

Habitual Physical Activity After Total Knee Replacement:analysis in 830 patients and comparison with a sex-and age-matched normative population (vol 92, pg 1109, 2012)

Background. Previous studies on physical activity after total knee arthroplasty (TKA) concentrated mainly on a return to sports activities. Objective. The objectives of this study were to determine the habitual physical activity behavior of people who had undergone TKA (TKA group) 1 to 5 years after surgery and to examine to what extent they adhered to international guidelines for health-enhancing physical activity. Additional aims were to compare younger (= 65 years old) people as well as men and women in the TKA group and to compare the results for the TKA group with those for a sex- and age-matched normative population (normative group). Design. This investigation was a cohort study. Methods. All people who had a primary TKA at 1 of 2 participating hospitals between 2002 and 2006 were sent the Short Questionnaire to Assess Health-Enhancing Physical Activity at least 1 year after surgery. Results. The TKA group spent, on average, 1,347 minutes per week on physical activity, most of which was light-intensity activity (780 minutes per week). Participants younger than 65 years of age spent significantly more time on physical activity than participants 65 years of age or older. There was no significant difference between male and female participants. Compared with the sex- and age-matched normative group, the TKA group spent significantly less time on the total amount of physical activity per week and met the guidelines for health-enhancing physical activity less often (55% versus 64%). Limitations. A self-administered questionnaire was used to assess habitual physical activity, and presurgery data on physical activity were not available. Conclusions. Almost half of the TKA group did not meet the health-enhancing physical activity guidelines, and the TKA group was not as physically active as the normative group. People who have undergone TKA should be encouraged to be more physically active

Folding, Design and Determination of Interaction Potentials Using Off-Lattice Dynamics of Model Heteropolymers

We present the results of a self-consistent, unified molecular dynamics study of simple model heteropolymers in the continuum with emphasis on folding, sequence design and the determination of the interaction parameters of the effective potential between the amino acids from the knowledge of the native states of the designed sequences.Comment: 8 pages, 3 Postscript figures, uses RevTeX. Submitted to Physical Review Letter

Elevation of plasma phospholipid transfer protein in transgenic mice increases VLDL secretion

Two lipid transfer proteins are active in human plasma, cholesteryl ester transfer protein (CETP), and phospholipid transfer protein (PLTP). Mice by nature do not express CETP. Additional inactivation of the PLTP gene resulted in reduced secretion of VLDL and subsequently in decreased susceptibility to diet-induced atherosclerosis. The aim of this study is to assess possible effects of differences in PLTP expression on VLDL secretion in mice that are proficient in CETP and PLTP. We compared human CETP transgenic (huCETPtg) mice with mice expressing both human lipid transfer proteins (huCETPtg/huPLTPtg). Plasma cholesterol in huCETPtg mice was 1.5-fold higher compared with huCETPtg/huPLTPtg mice (P < 0.001). This difference was mostly due to a lower HDL level in the huCETPtg/huPLTPtg mice, which subsequently could lead to the somewhat decreased CETP activity and concentration that was found in huCETPtg/huPLTPtg mice (P < 0.05). PLTP activity was 2.8-fold increased in these animals (P < 0.001). The human PLTP concentration was 5 microg/ml. Moderate overexpression of PLTP resulted in a 1.5-fold higher VLDL secretion compared with huCETPtg mice (P < 0.05). The composition of nascent VLDL was similar in both strains. These results indicate that elevated PLTP activity in huCETPtg mice results in an increase in VLDL secretion. In addition, PLTP overexpression decreases plasma HDL cholesterol as well as CETP

Neuropathic-like symptoms and the association with joint-specific function and quality of life in patients with hip and knee osteoarthritis

Objective There is an association between osteoarthritis-related pain severity and function, yet clear evidence about the sole influence of neuropathic-like symptoms on joint function and health-related quality of life (HRQoL) is lacking. Previous studies among knee OA patients show an association between neuropathic-like symptoms, lower functional status and lower quality of life, however analyses were unadjusted or had limited adjustment for influential covariates like pain intensity. The aim of this study was therefore to determine the influence of neuropathic-like symptoms-adjusted for multiple influential covariates-on joint-specific function and HRQoL in hip and knee OA patients. Methods In this observational study 255 patients (117 with hip OA and 138 with knee OA) completed the modified painDETECT questionnaire (mPDQ) to identify subjects with neuropathic-like symptoms (mPDQ score>12, possible neuropathic pain [NP] phenotype). The WOMAC and the RAND-36 were used to asses respectively function and HRQoL. Results were adjusted stepwise for age, sex and BMI (Model 1); back disorder, painful body regions, comorbidities and previous surgery (Model 2); and pain intensity and analgesic usage (Model 3). Results A possible NP phenotype was experienced by 37% of hip and 46% of knee OA patients. Final model 3 analysis revealed that hip OA patients with neuropathic-like symptoms scored significantly lower on pain-related aspects of HRQoL (GRAND-36 bodily pain: 6.8 points, p = 0.047) compared to patients with the unlikely NP phenotype. In knee OA patients, a possible NP phenotype was associated with diminished joint function (AWOMAC domains ranging 7.1 to 10.5 points, p Conclusion Neuropathic-like symptoms deteriorate the subjective rating of pain-related quality of life in hip OA patients and significantly influence function in knee OA patients