Lipoprotein lipase activity does not predict very low-density lipoprotein-triglyceride fatty acid oxidation during exercise.

Exercise lowers plasma triglyceride levels, but the physiological mechanisms remain not fully elucidated. Lipoprotein lipase (LPL) is a key enzyme in facilitating fatty acid uptake from lipoproteins. As exercise increases the efficiency of very low-density lipoprotein-triglyceride (VLDL-TG) oxidation, we hypothesized that muscle LPL activity would be a rate-limiting step and predict VLDL-TG Fatty acids oxidation during exercise. Sixteen healthy, lean subjects (eight men and eight women) were examined before and during an acute exercise bout (90 minutes at 50% of VO2-max). Heparin-releasable LPL activity was measured in muscle and adipose tissue biopsies. Breath 14 CO2 was measured after a primed-constant infusion of ex vivo labeled [14 C]-triolein VLDL-TG. Fractional VLDL-TG storage was measured in adipose tissue biopsies. Exercise did not affect muscle LPL activity (P=.30). No association was observed between muscle LPL activity and VLDL-TG oxidation, neither in the basal state (P=.17) nor during exercise (P=.83). Exercise did not affect upper body or lower body adipose tissue LPL activity (both P=.92). The basal adipose tissue fractional VLDL-TG storage (abdominal.13%±9%; femoral 17%±10% (P=.18)) was not associated with upper body (P=.56) or lower body (P=.44) subcutaneous adipose tissue LPL activity. Muscle LPL activity does not predict VLDL-TG oxidation during rest or exercise. In addition, adipose tissue LPL activity was not associated with VLDL-TG storage during rest. This suggests that LPL activity is present in excess of what is required to facilitate lipid uptake for oxidation during both rest and exercise.

A Nordic survey of management practices and owners' attitudes towards keeping horses in groups.

Keeping horses in groups is widely recommended but limited information is available about how this is implemented in practice. The aim of this survey was to describe how horses are kept in the Nordic countries in relation to sex, age, breed, and equestrian discipline and to assess owners' attitudes toward keeping horses in groups. Horse owners in Denmark, Finland, Norway, and Sweden were approached using a web-based questionnaire, which was translated into 4 languages and distributed online via equestrian forums, organizations, and social media. The number of respondents was 3,229, taking care of 17,248 horses. Only 8% of horses were never kept in groups, 47% were permanently grouped for 24 h/d, and 45% were stabled singly but grouped during turnout. Yearlings were most often permanently kept in groups (75%), mares and geldings more commonly during parts of the day (50 and 51%, respectively), and stallions were often kept alone (38%). Icelandic horses were more likely to be permanently kept in groups (36%) than warmbloods (16%) and ponies (15%). Twice as many competition horses (51%) were never grouped compared with horses used for breeding (20%) or leisure purposes (15%). The majority of respondents (86%) strongly agreed that group housing benefits horse welfare and that it is important for horses to have the company of conspecifics (92%). Nevertheless, not all horses were kept in groups, showing that attitudes toward group housing may not necessarily reflect current management. The risk of injury was a concern of many respondents (45%), as was introducing unfamiliar horses into already established groups (40%) and challenges in relation to feeding in groups (44%). Safety of people (23%) and difficulties handling group-kept horses (19%) were regarded as less problematic. Results suggest that the majority of horses have the possibility to freely interact with other horses, either as fulltime members of a group during 24 h/d or during turnout. Future research should address the extent to which being a part-time member of a group affects horse welfare. For permanent group housing to become more widespread, such as it is the case for most farm animals, future research could focus on solving some of the reoccurring problems perceived with keeping horses in groups. The dissemination of evidence-based information on all aspects around keeping horses in groups can ultimately stimulate further positive changes in the management of group-kept horses.

Enhanced Humoral Responses Induced by Targeting of Antigen to Murine Dendritic Cells.

Dendritic cells (DCs) are superior in their ability to induce and control adaptive immune responses. These qualities have motivated the hypothesis that targeted delivery of antigen to DCs in vivo may be an effective way of enhancing immunization. Recent results show that antigen targeted to certain DC surface molecules may indeed induce robust immune responses. Targeting of antigen to DCs can be accomplished by the means of monoclonal antibodies. This study compared the humoral responses induced in mice by in vivo targeting of DCs using monoclonal antibodies specific for CD11c, CD36, CD205, Clec6A, Clec7A, Clec9A, Siglec-H and PDC-TREM. The results demonstrate that antigen delivery to different targets on DCs in vivo gives rise to humoral responses that differ in strength. Targeting of antigen to CD11c, CD36, CD205, Clec6A, Clec7A and PDC-TREM induced significantly stronger antibody responses compared to non-targeted isotype-matched controls. Targeting of Clec9A and Siglec-H did not lead to efficient antibody responses, which may be due to unfavourable properties of the targeting antibody, in which case, other antibodies with the same specificity might elicit a different outcome. Anti-CD11c was additionally used for elucidating the impact of the route of vaccination, and the results showed only minor differences between the antibody responses induced after immunization either s.c., i.v. or i.p. Altogether, these data show that targeting of different surface molecules on DCs result in very different antibody responses and that, even in the absence of adjuvants, strong humoral responses was induced.

Chronic adrenergic stimulation induces brown adipose tissue differentiation in visceral adipose tissue.

BACKGROUND: Recruitment of brown adipose tissue is a promising strategy to treat obesity and Type 2 diabetes, but the physiological effects of a large amount of metabolically active brown adipose tissue in humans are unknown. CASE REPORT: In the present paper, we report a case of massive brown adipose tissue infiltration of the visceral adipose tissue depot in a person with Type 2 diabetes with a catecholamine-secreting paraganglioma. The patient was evaluated with [18F]-fludeoxyglucose positron emission tomography/computed tomography on three occasions: pre-therapy, during α-blockade and postoperatively. During surgery, biopsies of visceral and subcutaneous adipose tissue were obtained and evaluated for brown adipose tissue. At diagnosis, brown adipose tissue glucose uptake, assessed by [18F]-fludeoxyglucose-positron emission tomography, was massively increased. [18F]-fludeoxyglucose uptake was confined to known locations for brown adipose tissue, with additional uptake in the visceral adipose tissue. As a result of increased thermogenesis, resting energy expenditure was doubled. After surgical removal of the tumour, antidiabetic medicine was no longer needed, despite an 8.2-kg weight gain. CONCLUSION: These results show that human visceral adipose tissue holds an unprecedented potential for brown adipogenic differentiation; however, a detrimental effect on glucose metabolism persisted despite massive brown adipose tissue activity, with a doubling of resting energy expenditure.

Endothelial dysfunction after non-cardiac surgery: a systematic review.

BACKGROUND: More than 50% of patients with increased troponin levels after non-cardiac surgery have an impaired endothelial function pre-operatively. Non-invasive markers of endothelial function have been developed for the assessment of endothelial dysfunction. The aim of this paper was to systematically review the literature to evaluate the association between non-cardiac surgery and non-invasive markers of endothelial function. METHODS: A systematic search was conducted in MEDLINE, EMBASE and Cochrane Library Database according to the PRISMA guidelines. Endothelial dysfunction was described only with non-invasive measurements done both pre- and post-operatively and published in English. All types of non-cardiac surgery and both men and women of all ages were included. RESULTS: We found 1722 eligible studies in our search, and of these, five studies fulfilled our inclusion and exclusion criteria. Endothelial function was disturbed in patients after non-cardiac surgery. Three studies found a significant decrease in the endothelial function immediately after surgery (2 and 24 h post-operatively). Two studies found that patients with previous endothelial dysfunction and scheduled for surgery (renal transplantation and vascular surgery respectively) had an improvement in endothelial dysfunction 1 month after surgery. CONCLUSION: Endothelial function changes in relation to surgery. Assessment of endothelial function by non-invasive measures has the potential to guide clinicians in the prevention or treatment of post-operative myocardial damage.

Postprandial VLDL-triacylglycerol secretion is not suppressed in obese type 2 diabetic men.

AIMS/HYPOTHESIS: Type 2 diabetes is characterised by insulin resistance and increased post-absorptive secretion of VLDL-triacylglycerol (VLDL-TAG). Whether postprandial suppression of endogenous VLDL-TAG secretion is abnormal--a finding that would link hyperlipidaemia and type 2 diabetes--remains unclear. METHODS: Eight type 2 diabetic men and eight healthy men were studied before and after a fat-free test meal (40% of resting energy expenditure). VLDL-TAG kinetics were assessed using a primed-constant infusion of ex vivo labelled [1-(14)C]triolein VLDL-TAG using non-steady-state calculations. RESULTS: Type 2 diabetic men had a higher basal VLDL-TAG secretion rate and concentration than healthy men (mean ± SD secretion rate 137 ± 61 vs 78 ± 30 µmol/min, respectively [p = 0.03]; median concentration 1.03 [range 0.58-1.75] vs 0.33 [0.13-1.14] mmol/l, respectively [p < 0.01]). Postprandially, the VLDL-TAG secretion rate decreased in healthy men (p < 0.01), but remained unchanged in diabetic men (p = 0.47). The VLDL-TAG concentration increased in diabetic men and decreased in healthy men postprandially (p < 0.05). The difference in VLDL-TAG secretion rate between the two groups approached significance (p = 0.06) and the relative change in VLDL-TAG secretion rate was significantly different (p = 0.01) between the two groups. Basal VLDL-TAG clearance was significantly lower in diabetic men (diabetic men 133 [49-390] ml/min; healthy controls 215 [137-933] ml/min [p < 0.05]). After meal ingestion, clearance decreased in healthy men (p = 0.03), but was unchanged in diabetic men (p = 0.58). CONCLUSIONS/INTERPRETATION: Obese type 2 diabetic men have impaired postprandial suppression of VLDL-TAG secretion compared with lean healthy men, contributing to their postprandial lipaemia and hypertriacylglycerolaemia.

Body composition determines direct FFA storage pattern in overweight women.

Direct FFA storage in adipose tissue is a recently appreciated pathway for postabsorptive lipid storage. We evaluated the effect of body fat distribution on direct FFA storage in women with different obesity phenotypes. Twenty-eight women [10 upper body overweight/obese (UBO; WHR >0.85, BMI >28 kg/m(2)), 11 lower body overweight/obese (LBO; WHR <0.80, BMI >28 kg/m(2)), and 7 lean (BMI <25 kg/m(2))] received an intravenous bolus dose of [9,10-(3)H]palmitate- and [1-(14)C]triolein-labeled VLDL tracer followed by upper body subcutaneous (UBSQ) and lower body subcutaneous (LBSQ) fat biopsies. Regional fat mass was assessed by combining DEXA and CT scanning. We report greater fractional storage of FFA in UBSQ fat in UBO women compared with lean women (P < 0.01). The LBO women had greater storage per 10(6) fat cells in LBSQ adipocytes compared with UBSQ adipocytes (P = 0.04), whereas the other groups had comparable storage in UBSQ and LBSQ adipocytes. Fractional FFA storage was significantly associated with fractional VLDL-TG storage in both UBSQ (P < 0.01) and LBSQ (P = 0.03) adipose tissue. In conclusion, UBO women store a greater proportion of FFA in the UBSQ depot compared with lean women. In addition, LBO women store FFA more efficiently in LBSQ fat cells compared with UBSQ fat cells, which may play a role in development of their LBO phenotype. Finally, direct FFA storage and VLDL-TG fatty acid storage are correlated, indicating they may share a common rate-limiting pathway for fatty acid storage in adipose tissue.

Pharmacokinetics following continuous subcutaneous insulin infusion of insulin aspart with or without initial subcutaneous bolus.

AIM: To evaluate time to steady state insulin concentration (C(ss)) following continuous subcutaneous insulin infusion (CSII) of insulin aspart (IAsp) with or without an initial s.c. bolus. METHODS: In random order 10 healthy volunteers were given a basal insulin infusion rate (0.5 U/h) for 8 h with or without an initial s.c. bolus (1.4 U). Serum IAsp was measured until 3 h after infusion was stopped. RESULTS: An overshoot of IAsp was seen before C(ss) was achieved following an initial bolus of insulin as compared to no bolus. The apparent half-life (t((1/2))) with or without bolus did not differ (p = 0.15). Time to steady state (T(ss)) was evaluated in two ways: (1) T(ss) defined as the first point within an interval of C(ss)+/- 2 x CV was 233 vs. 166 min with and without a bolus respectively (p = 0.068). (2) A t-test was performed for each concentration-time point vs. mean C(ss), and the first point with no significance was defined, T(ss). This gave 208 (p = 0.09) and 178 min (p = 0.24) with and without bolus respectively. Mathematical modelling suggests that an ideal mean bolus should be 0.89 U, and that this bolus dose may result in a shorter T(ss). CONCLUSION: A bolus of 1.4 U resulted in an overshoot of serum IAsp before C(ss) and a longer period before C(ss) is achieved. Mathematical modelling suggests that a mean bolus of 0.89 U would result in a faster achievement of C(ss) compared to no bolus.

Visceral fat mass is a strong predictor of circulating ghrelin levels in premenopausal women.

OBJECTIVE: A well known inverse relationship exists between obesity and circulating ghrelin concentrations. However, obesity is a heterogeneous disease entity and upper-body obesity (UBO) is associated with more profound metabolic disturbances than lower-body obesity (LBO). We therefore aimed to investigate the impact of body composition on circulating ghrelin levels in women spanning a wide range of body composition phenotypes. SUBJECTS AND METHODS: Ten (UBO; waist-to-hip ratio (WHR) >0.85, body mass index (BMI) >28 kg/m(2)), ten LBO (WHR <0.80, BMI >28 kg/m(2)) and ten lean women (BMI<25 kg/m(2)) were studied. Total ghrelin levels were measured under basal and hyperinsulinemic (0.6 mU/kg per min) conditions. Body fat distribution was determined by dual X-ray absorptiometry in combination with computed tomography at the L2-L3 level. RESULTS: As expected, an inverse correlation existed between basal ghrelin concentration and BMI (r=-0.40, P=0.03) and total fat mass (r=-0.39, P=0.04). Visceral fat mass was a strong predictor (r=-0.56, P=0.003) of circulating ghrelin levels, even when adjusted for BMI (P=0.02) or body composition group (P=0.04). The suppressive effect of insulin on ghrelin concentration was significantly diminished in the UBO compared with the lean controls (P=0.012) and a highly significant inverse correlation existed with visceral fat mass (r=-0.52, P=0.004). CONCLUSIONS: Visceral fat mass is a strong predictor of basal ghrelin concentrations and also attenuates the suppressive effect of insulin on ghrelin concentrations. These data provide further evidence that the UBO phenotype is associated with more profound metabolic abnormalities than obesity per se.

Color M-mode and pulsed wave tissue Doppler echocardiography: powerful predictors of cardiac events after first myocardial infarction.

To assess the association between color M-mode flow propagation velocity and the early diastolic mitral annular velocity (E(m)) obtained with tissue Doppler echocardiography and to assess the prognostic implications of the indexes, echocardiography was performed on days 1 and 5, and 1 and 3 months after a first myocardial infarction in 67 consecutive patients. Flow propagation velocity correlated well with E(m) (r = 0.72, P <.0001). The ratio of peak E-wave velocity (E) to flow propagation velocity also correlated well with E/E(m) (r = 0.87, P <.0001). The positive predictive value of E/FPV > or =1.5 to identify patients with Killip class > or =II was 90%, and the negative predictive value 92%. The corresponding values for E/E(m) > or =10 were 70% and 90%. Cox proportional hazards analysis identified E/flow propagation velocity > or =1.5 (relative risk, 12.4 [95% confidence interval, 4.1-37.3]), E/E(m) > or =10 (relative risk, 11.5 [95% confidence interval, 3.8-34.7]), and Killip class > or =II (relative risk, 7.8 [95% confidence interval, 1.6-40.4]) to be predictors of the composite end point of cardiac death and readmission because of heart failure. Thus flow propagation velocity and E(m) are closely related after myocardial infarction and appear to have similar prognostic information.

The Doppler echocardiographic myocardial performance index predicts left-ventricular dilation and cardiac death after myocardial infarction.

To investigate the value of the Doppler-derived myocardial performance index to predict early left-ventricular (LV) dilation and cardiac death after a first acute myocardial infarction (AMI), Doppler echocardiography was performed within 24 h of hospital admission, on day 5, 1 and 3 months after AMI in 125 consecutive patients. The index measured on day 1 correlated well with the change in end-diastolic volume index observed from day 1 to 3 months following AMI (r = 0.66, p < 0.0001). One-year survival in patients with Doppler index <0.63 was 89%, and 37% in patients with index > or = 0.63, (p < 0.0001). Multivariate analysis identified myocardial performance index > or = 0.63 (relative risk 5.6, p < 0.0001), E-wave deceleration time <140 ms (relative risk 2.7, p = 0.008) and Killip class > or = II (relative risk 4.0, p = 0.04) to be independent predictors of cardiac death. Therefore, we conclude that the Doppler echocardiographic myocardial performance index is a predictor of LV dilation and cardiac death after a first AMI.

Serial Doppler echocardiographic assessment of left and right ventricular performance after a first myocardial infarction.

We sought to investigate the relation between left ventricular (LV) and right ventricular (RV) function assessed with the Doppler-derived myocardial performance index (MPI), to assess serial changes, and to investigate the prognostic value of biventricular assessment of cardiac function after a first myocardial infarction (MI). To do so, serial Doppler echocardiography was performed in 77 consecutive patients with a first MI. Right ventricular MPI correlated significantly with LV MPI (r = 0.51, P <.0001). In patients with echocardiographic signs of RV MI, the RV MPI was significantly higher (0.59 +/- 0.18 versus 0.44 +/- 0.19, P =.001), whereas no difference in LV MPI was seen (0.55 +/- 0.19 versus 0.56 +/- 0.13, P = not significant). Right ventricular MPI showed a rapid normalization during follow-up, whereas LV MPI did not decrease. During follow-up, 23 patients died of cardiac causes or were readmitted because of worsening heart failure. Multivariate Cox analysis indicated LV MPI (relative risk 4.9 [95% CI 1.8-13.5], P =.002) and RV MPI (relative risk 3.8 [1.3-17.0], P =.01) to be predictors of cardiac events. Thus the RV MPI is frequently abnormal after a first MI but normalizes rapidly on follow-up, and biventricular assessment of cardiac function may improve the prognostic accuracy compared with LV assessment alone.

Pseudonormal and restrictive filling patterns predict left ventricular dilation and cardiac death after a first myocardial infarction: a serial color M-mode Doppler echocardiographic study.

OBJECTIVES: We sought to assess the prognostic value of left ventricular (LV) filling patterns, as determined by mitral E-wave deceleration time (DT) and color M-mode flow propagation velocity (Vp), on cardiac death and serial changes in LV volumes after a first myocardial infarction (MI). BACKGROUND: Combined assessment of DT and Vp allows separation of the effects of compliance and relaxation on LV filling, thereby allowing identification of pseudonormal filling. This may be valuable after MI, where abnormal LV filling is frequently present. METHODS: Echocardiography was performed within 24 h, five days and one and three months after MI in 125 unselected consecutive patients. Normal filling was defined as DT 140 to 240 ms and Vp > or =45 cm/s; impaired relaxation as DT > or =240 ms; pseudonormal filling as DT 140 to 240 ms and Vp <45 cm/s; and restrictive filling as DT <140 ms. RESULTS: Left ventricular filling was normal in 38 patients; impaired relaxation in 38; pseudonormal in 23; and restrictive in 26. End-systolic and end-diastolic volume indexes were significantly increased during the first three months after MI in patients with pseudonormal or restrictive filling (37+/-15 vs. 47+/-19 ml/m2, p<0.0005 and 71+/-20 vs. 88+/-24 ml/m2, p<0.0005, respectively). During a follow-up period of 12+/-7 months, 33 patients died. Mortality was significantly higher in patients with impaired relaxation (p = 0.02), pseudonormal filling (p<0.00005) and restrictive filling (p<0.00005), compared with patients with normal filling. On Cox analysis, restrictive filling (p = 0.003), pseudonormal filling (p = 0.006) and Killip class > or =II (p = 0.008) independently predicted cardiac death, compared with clinical and echocardiographic variables. CONCLUSIONS: Pseudonormal or restrictive filling patterns are related to progressive LV dilation and predict cardiac death after a first MI.

Preload dependence of color M-mode Doppler flow propagation velocity in controls and in patients with left ventricular dysfunction.

The purpose of this study was to assess the effects of preload alterations on color M-mode flow propagation velocity (Vp) in volunteers with normal left ventricular (LV) function and in patients with depressed LV function. Color M-mode Doppler echocardiography was performed during Valsalva maneuver, passive leg lifting, and after administration of nitroglycerin in 30 healthy volunteers and in 30 age- and sex-matched patients with previous myocardial infarction (MI). Mean Vp in controls was 74 +/- 15 cm/s at baseline and 46 +/- 15 cm/s in MI patients (P <.0005). In both groups, minor changes in Vp were seen during preload alterations; however, these were not significant (control P =.72, MI P =.31). In both groups, peak E-wave velocity (P <.0005), ratio of early-to-late peak velocities (P <.0005), and E-wave deceleration time (P <.0005) were found to change during preload alterations. In conclusion, we found that in controls and patients with previous MI, the color M-mode flow propagation velocity is not affected significantly by preload.

Ratio of left ventricular peak E-wave velocity to flow propagation velocity assessed by color M-mode Doppler echocardiography in first myocardial infarction: prognostic and clinical implications.

OBJECTIVES: To determine the ability of the ratio of peak E-wave velocity to flow propagation velocity (E/Vp) measured with color M-mode Doppler echocardiography to predict in-hospital heart failure and cardiac mortality in an unselected consecutive population with first myocardial infarction (MI). BACKGROUND: Several experimental studies indicate color M-mode echocardiography to be a valuable tool in the evaluation of diastolic function, but data regarding the clinical value are lacking. METHODS: Echocardiography was performed within 24 h of arrival at the coronary care unit in 110 consecutive patients with first MI. Highest Killip class was determined during hospitalization. Patients were divided into groups according to E/Vp <1.5 and > or =1.5. RESULTS: During hospitalization 53 patients were in Killip class > or =II. In patients with E/Vp > or =1.5, Killip class was significantly higher compared with patients with E/Vp <1.5 (p < 0.0001). Multivariate logistic regression analysis identified E/Vp > or =1.5 to be the single best predictor of in-hospital clinical heart failure when compared with age, heart rate, E-wave deceleration time (Dt), left ventricular (LV) ejection fraction, wall motion index, enzymatic infarct size and Q-wave MI. At day 35 survival in patients with E/Vp <1.5 was 98%, while for patients with E/Vp > or =1.5, it was 58% (p < 0.0001). Cox proportional hazards model identified Dt <140 ms, E/Vp > or =1.5 and age to be independent predictors of cardiac death, with Dt < 140 ms being superior to age and E/Vp. CONCLUSIONS: In the acute phase of MI, E/Vp > or =1.5 measured with color M-mode echocardiography is a strong predictor of in-hospital heart failure. Furthermore, E/Vp is superior to systolic measurements in predicting 35 day survival although Dt <140 ms is the most powerful predictor of cardiac death.

Oesophageal peristalsis. A simple system for the recording of oesophageal peristalsis, and the influence of bolus volume on peak peristaltic pressure amplitude.

Peak oesophageal peristaltic pressure amplitude was recorded in 8 healthy subjects at points 5 and 15 cm proximal to the gastro-oesophageal sphincter, by using an in situ tip-transducer simultaneously with a continuous flush (Intraflo) perfused catheter system with external pressure transducer. Dry swallows and wet swallows of 2.5, 5 and 10ml, respectively, were made in random succession. In all cases the pressures recorded by either system correlated well. In all cases the peristaltic pressure amplitude was significantly higher after the wet swallows. The catheter and flow system used in this study is simple and makes recording of peristaltic pressures independent of the shape of the in situ transducer, and its therefore well suited for measuring the amplitude of oesophageal contractions.