[Change Mechanisms in Group Therapy: A Questionnaire to Measure Therapeutic Perspectives]. / Wirkfaktoren in der Gruppentherapie: Fragebogen zur Messung der therapeutischen Perspektive.

Group therapy was shown to be an effective and economic intervention. To date few instruments exist to empirically assess mechanisms of therapeutic change in group therapy. The Group Therapy Process Questionnaire for Therapists (FEPiG-T) measuring change mechanisms in group therapy as viewed from the perspectives of therapists was developed and validated in this study based on the conceptualizations of Grawe,Yalom and Bordin and in reference to the previously developed measure for patients. The FEPiG-T subscales show good internal consistencies and small to large correlations with convergent measures. Subscales at beginning of therapy correlated with improvement of interpersonal problems over time. Further associations with symptom scales remained more vague. However, intersections with the established version for patients allow routinely implemented evaluation of the 2 perspectives in clinical practice, but inevitably need careful interpretation where the instruments differ in their factor structure.

Increasing the treatment motivation of patients with somatic symptom disorder: applying the URICA-S scale.

BACKGROUND: Therapeutic intervention programs for somatic symptom disorder (SSD) show only small-to-moderate effect sizes. These effects are partly explained by the motivational problems of SSD patients. Hence, fostering treatment motivation could increase treatment success. One central aspect in SSD patients might be damage to motivation because of symptomatic relapses. Consequently, the aim of the present study was to investigate associations between motivational relapse struggle and therapeutic outcome in SSD patients. METHODS: We assessed 84 inpatients diagnosed with SSD in the early, middle and late stages of their inpatient treatment. The maintenance subscale of the University of Rhode Island Change Assessment-Short (URICA-S) was applied as a measure to assess motivational relapse struggle. Additionally, patients completed measures of treatment outcome that focus on clinical symptoms, stress levels and interpersonal functioning. RESULTS: The results from multiple regression analyses indicate that higher URICA-S maintenance scores assessed in early stages of inpatient treatment were related to more negative treatment outcomes in SSD patients. CONCLUSIONS: SSD patients with ambivalent treatment motivation may fail in their struggle against relapse over the course of therapy. The URICA-S maintenance score assessed at therapy admission facilitated early identification of SSD patients who are at greater risk of relapse. Future studies should incorporate randomized controlled trials to investigate whether this subgroup could benefit from motivational interventions that address relapse.

Human pharmacokinetics of intravenous recombinant human Cu/Zn superoxide dismutase.

OBJECTIVE: Oxidative stress plays an important role in human disease, but antioxidant therapies are limited. Under physiological conditions superoxide is controlled by the enzyme superoxide dismutase. A recombinant human Cu/Zn superoxide dismutase (rhSOD) might open new therapeutic possibilities. METHODS: Safety profile and pharmacokinetics in plasma and urine were assessed in an open label phase I study with dose-escalation. 18 healthy male volunteers received a single intravenous 10-minute infusion of 150, 300, or 600 mg rhSOD, respectively (n = 6 per dose group). RESULTS: rhSOD was well tolerated. Peak plasma concentrations (cmax; mean ± SD) were reached at the end of infusion, with 32.96 ± 10.31, 51.60 ± 8.23, and 103.90 ± 19.02 µg/ ml, respectively. Non-compartmental halflife was 1.06 ± 0.37, 1.59 ± 0.64, and 1.63 ± 0.28 hours. Urinary excretion (10 h) showed dose-dependent relative increases with 11.28 ± 6.46 (7.5%), 54.93 ± 15.25 (18.3%), and 191.81 ± 104.60 mg (32.0%). CONCLUSIONS: Our results show a good safety profile and predictable pharmacokinetics of rhSOD, suggesting that therapeutic exploratory studies might be safely conducted in humans.

Vascular function in obese children with non-alcoholic fatty liver disease.

OBJECTIVE: To test whether obese children with non-alcoholic fatty liver disease have impaired vascular function compared with obese children with normal liver fat content. METHODS: Obese children (n = 28, 16 males, mean age 10.9 ± 0.7 years, body mass index [BMI] 31.9 ± 4.5 kg/m(2)) with normal (HCLn) and increased hepatocellular lipid content (HCLi, 2.6 ± 0.8 vs. 12.4 ± 8.2%) were recruited, outcome measures being flow-mediated dilation of the brachial artery [FMD] measured by ultrasound, biochemical markers of inflammation (hs-CRP, hs-IL6) and cell adhesion molecules [CAMs], hepatocellular lipids, visceral and subcutaneous fat quantified by nuclear magnetic resonance spectroscopy and imaging. RESULTS: HCLi and HCLn groups showed no significant differences in terms of age, gender, BMI, waist circumference and subcutaneous fat. Subjects in the HCLi group had significantly higher amounts of visceral fat and higher fasting glucose, insulin and triglyceride, but lower adiponectin levels and were more insulin resistant than their HCLn controls. Hepatic fat fraction (HFF) correlated positively with fasting plasma glucose, HOMA-IR, adiponectin, visceral fat, negatively with WBISI independent of BMI. HFF was not associated with subcutaneous fat, fasting insulin, FFA, HDL-C, TG, hs-CRP, hs-IL6, vCAM, iCAM, and FMD. HCLi patients had significantly higher serum levels of hs-CRP and hs-IL6 than HCLn controls. FMD and serum levels of vCAM and iCAM were comparable between groups. CONCLUSIONS: Obese children with simple steatosis rather than steatohepatitis seem to have intact vascular function. Further studies in obese children with different grades of NAFLD are warranted to elucidate the role of fatty liver as a marker of risk for future cardiovascular events.

YKL-40 concentrations are not elevated in gestational diabetes.

BACKGROUND: Gestational diabetes (GDM) is an increasing and common complication of pregnancy. The involvement of inflammatory mechanisms in GDM remains unclear. YKL-40 is a novel inflammatory marker that has been recently found to be associated with type 2 diabetes. This is the first study to investigate YKL-40 in GDM. MATERIAL AND METHODS: A total of 58 subjects were included, 28 patients with GDM (BMI 33.2 +/- 6.1 kg m(-(2)), 33 +/- 6 years) and 30 healthy pregnant controls (BMI 28.4 +/- 5.2 kg m(-(2)), 33 +/- 4 years; mean +/- SD). Standard risk factors for GDM (weight and BMI prior to pregnancy, family history, former GDM, high birthweight offspring) were evaluated. A 2-h 75-g oral glucose tolerance test (oGTT) and measurement of YKL-40 were conducted in gestational week 28 +/- 4, as well as 8 weeks after delivery. RESULTS: YKL-40 was not different between GDM and controls, neither during (65.8 +/- 44.4 vs. 60.3 +/- 30.1 ng mL(-1)), nor after pregnancy (63.4 +/- 30.5 vs. 66.9 +/- 32.7 ng mL(-1)). YKL-40 was correlated with insulin, HOMA and BMI. GDM had higher fasting insulin (14.1 +/- 7.4 vs. 8.3 +/- 4.3 muU mL(-1)) and glucose (88 +/- 13 - 200 +/- 31 - 160 +/- 33 vs. 76 +/- 10 - 146 +/- 37 - 112 +/- 28 mg dL(-1) for fasting, 1- and 2-h-concentrations in the oGTT, respectively), higher HbA1c (5.3 +/- 0.4 vs. 5.0 +/- 0.5%;), HOMA (3.1 +/- 1.7 vs. 1.6 +/- 0.9), and BMI (33.2 +/- 6.1 vs. 28.5 +/- 5.2 kg m(-2)) (means +/- SD, all P < 0.01). CONCLUSIONS: No difference in YKL-40 between GDM and controls suggests similar inflammatory status at the time of measurements. The short duration of metabolic changes during GDM might explain this finding, which is in contrast to results in type 2 diabetes.

Increase of osteopontin plasma concentrations after bariatric surgery independent from inflammation and insulin resistance.

BACKGROUND: Osteopontin (OPN) is a multifunctional matrix glycoprotein associated with bone metabolism and has been linked to chronic inflammation, insulin resistance, and atherosclerosis. Diet-induced weight loss decreases elevated OPN concentrations in obese patients. The aim of the current study was to investigate the role of OPN after bariatric surgery, where not only improvements of chronic inflammation, insulin resistance and comorbidities, but also malabsorption and altered bone metabolism have been reported. METHODS: OPN plasma concentrations were determined in 31 morbidly obese patients (5 men, 26 women, BMI 46.2+/-7.1 kg/m2, age 41+/-11 years; mean+/-SD) before and 18 months after bariatric surgery, together with parameters of bone metabolism and inflammation. RESULTS: OPN concentrations increased by +20.3+/-26.6 ng/ml (mean+/-SD, p<0.01), concomitant to a weight loss of -38+/-22 kg, and a decrease in BMI by -13.1+/-7.7 kg/m2 (both p<0.01). HOMA-index improved from 5.2+/-3.4 to 1.5+/-1.0 (p<0.01). Calcium concentrations slightly decreased, and phosphate increased (-0.06+/-0.13 mmol/l and +0.08+/-0.16 mmol/l, respectively; both p<0.05), while 25-OH-Vitamin D3 remained unchanged and PTH tended to increase (+5.1+/-14.0 pg/ml, p=0.054). Monocyte chemoattractant protein 1 and interleukin 18 were significantly decreased and associated with HOMA both before and after bariatric surgery. DeltaOPN was correlated with DeltaPTH, but not with other parameters. CONCLUSIONS: OPN plasma concentrations increased concomitant to weight loss after bariatric surgery, which was independent from an improvement of insulin sensitivity and a decrease of inflammatory markers. Further studies are needed to differentiate whether these changes in bone metabolism after bariatric surgery are secondary to calcium deficiency or an adaptation to weight loss.

Intra-arterial vitamin C prevents endothelial dysfunction caused by ischemia-reperfusion.

OBJECTIVE: Ischemia-reperfusion (IR) injury causes tissue injury and endothelial dysfunction. There is evidence that oxidative stress plays an important role. METHODS: We tested if IR-induced endothelial dysfunction could be prevented by administration of the antioxidant vitamin C. Twenty-six healthy male subjects and eight male patients with peripheral arterial disease (PAD) were enrolled in this randomised placebo-controlled study. Forearm blood flow (FBF) measurements in response to the vasodilators acetylcholine (ACh; endothelium-dependent agonist) or nitroglycerin (NTG; endothelium-independent) were performed before and after forearm ischemia for 20 min. FBF responses were reassessed during reperfusion with intra-arterial co-administration of 24 mg/min vitamin C or placebo. In six volunteers responses to the NO-synthase inhibitor N-monomethyl-L-arginine (L-NMMA) were also assessed before and after ischemia with and without vitamin C. RESULTS: ACh-induced vasodilation was blunted in subjects receiving placebo after reperfusion (p<0.05 versus baseline). Administration of vitamin C completely prevented impaired responsiveness. NTG-induced vasodilation was not affected by reperfusion or vitamin C. This finding was consistent in patients with PAD and impaired endothelial function, where local vitamin C infusion restored FBF reactivity to ACh before and after IR injury (p<0.05 versus baseline). Again, NTG-induced vasodilation was not affected. Blunted L-NMMA responses seen during reperfusion could be completely reversed by vitamin C. CONCLUSIONS: Our data indicate that IR-induced vascular injury can be prevented by administration of antioxidants.

Impaired vascular nitric oxide bioactivity in women with previous gestational diabetes.

BACKGROUND: Dysfunction of the vascular endothelium, preceding vascular morbidity and type 2 diabetes, is present in women with previous gestational diabetes (GDM). However, it is unknown whether excess weight, insulin resistance, and asymmetric dimethylarginine (ADMA)--an endogenous nitric oxide (NO) synthase inhibitor--also contribute to the vascular changes observed in these patients. The aim of this study was therefore to identify factors other than GDM that impair vascular function. METHODS: Seven overweight and five non-overweight women with previous GDM were included in this study. Vascular function was assessed from forearm blood-flow responses to the endothelium-dependent vasodilator acetylcholine (ACh), the endothelium-independent vasodilator glyceryltrinitrate, the vasoconstrictor norepinephrine and the NO synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA). ADMA was measured in venous blood, and insulin resistance was estimated from a modified intravenous glucose tolerance test. Twenty healthy male volunteers served as a historical control group. RESULTS: Vasodilation of forearm resistance vessels in response to ACh was impaired in overweight women when compared with non-overweight women (P < 0.05); similarly, vasoconstrictor reactivity tended to be smaller in the overweight group. In addition, there was a significant relationship between vascular responsiveness to ACh and L-NMMA, body-mass index, serum ADMA concentrations and stimulated glucose levels (all P < 0.05). ACh responses and ADMA levels in non-overweight women were similar to those of healthy controls. CONCLUSION: Factors such as obesity, increased ADMA levels and insulin resistance appear to be strong contributors to endothelial dysfunction observed in women with GDM.

Effects of N-acetylcysteine against systemic and renal hemodynamic effects of endotoxin in healthy humans.

OBJECTIVE: Systemic inflammation causes vasodilation and impairs the vascular response to catecholamines. There is evidence that altered vasoreactivity is associated with increased production of free radicals. We studied the influence of systemic doses of the antioxidant N-acetylcysteine on inflammatory cytokines and renal plasma flow and on the systemic pressor response to norepinephrine during experimental endotoxemia. DESIGN: A double-blind, placebo-controlled crossover study. SETTING: Medical University of Vienna, Clinical Pharmacology, Vienna General Hospital, AKH. SUBJECTS: Eight healthy, male humans. INTERVENTIONS: Intravenous administration of Escherichia coli endotoxin (lipopolysaccharide, 20 IU/kg) on two separate study days with concomitant intravenous infusion of placebo or N-acetylcysteine (150 mg/kg loading dose; 15 mg/kg/hr continuous infusion), respectively. MEASUREMENTS AND MAIN RESULTS: Measurements of inflammatory cytokines, of renal plasma flow by the para-aminohippurate-clearance method, and of the systemic pressor response to norepinephrine were taken at baseline and after endotoxin. Lipopolysaccharide increased body temperature and plasma concentrations of tumor necrosis factor-alpha, which was mitigated during N-acetylcysteine infusions. Likewise, the lipopolysaccharide-induced increases in renal plasma flow and decreases in blood pressure were attenuated, and the hyporeactivity of pulse rate to norepinephrine 4 hrs after lipopolysaccharide was improved by N-acetylcysteine. CONCLUSION: High doses of N-acetylcysteine might exert protective effects on systemic hemodynamics and on the reactivity to catecholamines in humans challenged by lipopolysaccharide. This action of the antioxidant N-acetylcysteine is paralleled by humoral anti-inflammatory mechanisms and may be useful in patients with systemic inflammation.

Rosiglitazone prevents free fatty acid-induced vascular endothelial dysfunction.

CONTEXT: Free fatty acids (FFAs) cause insulin resistance and vascular endothelial dysfunction. The peroxisome proliferator-activated receptor gamma agonist rosiglitazone acts as insulin sensitizer and could exert vasoprotective properties by preservation of endothelium-dependent vasodilation. OBJECTIVE: We tested the effect of rosiglitazone on FFA-induced endothelial dysfunction of the forearm resistance vessels, insulin sensitivity, asymmetric dimethylarginine (ADMA), and high-sensitivity C-reactive protein concentrations in humans. DESIGN AND SETTING: We conducted a double-blind, randomized, placebo-controlled parallel-group study at a university hospital. PATIENTS AND INTERVENTIONS: Rosiglitazone 8 mg daily or placebo was administered to 16 healthy male subjects for 21 d. On the last day, triglycerides and heparin were infused iv to increase FFA plasma concentrations. MAIN OUTCOME MEASURES: Forearm blood flow responses to the endothelium-dependent vasodilator acetylcholine and the endothelium-independent vasodilator nitroglycerine were assessed using strain-gauge plethysmography at baseline, and on d 21 before and after 5 h of triglyceride/heparin infusion. RESULTS: Forearm blood flow reactivity was not affected by rosiglitazone or placebo. Infusion of triglyceride/heparin substantially increased FFA concentrations (P < 0.001) and reduced endothelium-dependent vasodilation by 38 +/- 17% (P = 0.024). In the face of lower FFA elevation (P = 0.047 vs. controls), endothelium-dependent vasodilation was preserved in subjects receiving rosiglitazone (P = 0.016 vs. placebo). Endothelium-independent vasodilation and C-reactive protein were unchanged, whereas insulin sensitivity and plasma ADMA similarly decreased in both study groups after FFA elevation (both P < 0.05 vs. baseline). CONCLUSIONS: Rosiglitazone mitigates the increase in FFA after infusion of triglyceride/heparin and prevents FFA-induced endothelial dysfunction. These effects are independent and possibly occur before any changes in insulin sensitivity and ADMA plasma concentrations in healthy subjects.

The adipokine visfatin is markedly elevated in obese children.

OBJECTIVE: The insulin-mimetic adipocytokine visfatin has been linked to adiposity and the metabolic syndrome. DESIGN: Cross-sectional study. SUBJECTS: Eighty-three nondiabetic obese children and 40 healthy controls. MEASUREMENTS: We analyzed plasma visfatin concentrations to assess whether this adipokine is associated with adiposity. RESULTS: Plasma visfatin concentrations were nearly 2-fold higher in obese children (mean, 1.1 ng/mL; 95% CI, 0.2-6.6) than in controls (0.6 ng/mL, 95% CI, 0.6 to 0.6; P < 0.001). No relationship was detectable between visfatin and other subject characteristics, hsCRP or the lipid profile. CONCLUSIONS: Visfatin may be involved in the development of metabolic derangements in obese children.

[Malign and refractory hypertension]. / Maligne und therapierefraktäre Hypertonie.

Early occurences of organ damage, mainly in the cardiovascular system, the central nervous system, of the kidney or the retina, are hallmarks of a malign course in arterial hypertension. Peracute hypertensive emergencies can lead to a rapid deterioration of organ functions, a slower development is observed in patients with therapy-resistant forms of arterial hypertension. In the following article we discuss the historical trends in terminology and epidemiology, clinical symptoms, and possible causes for therapy-resistant hypertension. The latter mainly focuses on possible secondary forms of hypertension and on thoughts on therapy-resistance in primary, idiopathic arterial hypertension, as well as on possible therapeutic approaches.

A proinflammatory state is detectable in obese children and is accompanied by functional and morphological vascular changes.

BACKGROUND: Obesity is generally accepted as a risk factor for premature atherosclerosis. Subclinical inflammation as quantified by blood levels of C-reactive protein (CRP) contributes to the development and progression of atherosclerosis. We hypothesized that inflammation in obese children is related to functional and early morphological vascular changes. METHODS AND RESULTS: Blood levels of high sensitivity (hs) CRP, hsIL-6, the soluble intercellular adhesion molecule1 (ICAM-1), vascular cell adhesion molecule (VCAM)-1, and E-selectin were measured in 145 severely obese (body mass index [BMI], 32.2+/-5.8 kg/m2) and 54 lean (BMI, 18.9+/-3.2 kg/m2) children 12+/-4 years old. Flow-mediated dilation (FMD) of the brachial artery and carotid intima-media thickness (IMT) measured by high-resolution ultrasound as markers of early vascular changes were assessed in 92 (77 obese and 15 lean) and 59 (50 obese and 9 lean) children, respectively. Obese children had significantly higher levels of hsCRP, hsIL-6, and E-selectin than healthy controls (4.1+/-4.8 versus 0.9+/-1.5 mg/L, P<0.001 for hsCRP; 1.99+/-1.30 versus 1.42+/-1.01 pg/mL, P=0.05 for hsIL-6; and 78+/-38 versus 59+/-29 ng/mL, P=0.01 for E-selectin). There were no differences in the levels of ICAM-1 and VCAM-1 between groups. Obese children had lower peak FMD response (7.70+/-6.14 versus 11.06+/-3.07%, P=0.006) and increased IMT (0.37+/-0.04 versus 0.34+/-0.03 mm, P=0.03) compared with controls. Morbidly obese children (n=14, BMI 44.1+/-3.9 kg/m2) had highest levels of hsCRP (8.7+/-0.7 mg/L), hsIL-6 (3.32+/-1.1 pg/mL), and E-selectin (83+/-40 ng/mL). CONCLUSIONS: A proinflammatory state is detectable in obese children, which is accompanied by impaired vascular endothelial function and early structural changes of arteries, even in young subjects at risk. It remains to be determined whether high hsCRP in obese children predicts cardiovascular events.

Free fatty acids normalize a rosiglitazone-induced visfatin release.

The detrimental effect of elevated free fatty acids (FFAs) on insulin sensitivity can be improved by thiazolidinediones (TZDs) in patients with type 2 diabetes mellitus. It is unknown whether this salutary action of TZD is associated with altered release of the insulin-mimetic adipocytokine visfatin. In this study, we investigated whether visfatin concentrations are altered by FFA and TZD treatment. In a randomized, double-blind, placebo-controlled, parallel-group study 16 healthy volunteers received an infusion of triglycerides/heparin to increase plasma FFA after 3 wk of treatment with rosiglitazone (8 mg/day, n = 8) or placebo (n = 8), and circulating plasma visfatin was measured. As a corollary, human adipocytes were incubated with synthetic fatty acids and rosiglitazone to assess visfatin release in vitro. The results were that rosiglitazone treatment increased systemic plasma visfatin concentrations from 0.6 +/- 0.1 to 1.7 +/- 0.2 ng/ml (P < 0.01). Lipid infusion caused a marked elevation of plasma FFA but had no effect on circulating visfatin in controls. In contrast, elevated visfatin concentrations in subjects receiving rosiglitazone were normalized by lipid infusion. In isolated adipocytes, visfatin was released into supernatant medium by acute addition and long-term treatment of rosiglitazone. This secretion was blocked by synthetic fatty acids and by inhibition of phosphatidylinositol 3-kinase or Akt. In conclusion, release of the insulin-mimetic visfatin may represent a major mechanism of metabolic TZD action. The presence of FFA antagonizes this action, which may have implications for visfatin bioactivity.

Increased plasma visfatin concentrations in morbidly obese subjects are reduced after gastric banding.

CONTEXT: The insulin-mimetic adipocytokine visfatin has been linked to obesity. The influence of weight loss on plasma visfatin concentrations in obese subjects is unknown yet. OBJECTIVES: In this study we investigated whether plasma visfatin concentrations are altered by weight loss in patients with obesity. DESIGN AND PATIENTS: In a prospective study, fasting plasma visfatin, leptin, and adiponectin concentrations were measured before and 6 months after gastric banding in 31 morbidly obese patients aged 40 +/- 11 yr with a body mass index (BMI) of 46 +/- 5 kg/m(2). Fourteen healthy subjects aged 29 +/- 5 yr with a BMI less than 25 kg/m(2) served as controls. RESULTS: Visfatin plasma concentrations were markedly elevated in obese subjects (0.037 +/- 0.008 microg/ml), compared with controls (0.001 +/- 0.000 microg/ml, P < 0.001). Gastric banding reduced BMI to 40 +/- 5 kg/m(2), visfatin to 19.2 +/- 10.9 ng/ml, and leptin from 39.0 +/- 12.4 to 29.7 +/- 10.0 ng/ml and increased adiponectin from 0.015 +/- 0.007 to 0.017 +/- 0.007 microg/ml (all P < 0.05) after 6 months. Insulin sensitivity as estimated by the homeostasis model assessment insulin resistance index was unchanged from 5.8 +/- 3.1 to 4.6 +/- 1.9 (P = 0.13), but individual changes of insulin resistance and visfatin were significantly associated (P < 0.05, r = -0.43). CONCLUSIONS: Elevated plasma visfatin concentrations in morbidly obese subjects are reduced after weight loss. This may be related to changes in insulin resistance over time.

Exercise training improves low-density lipoprotein oxidability in untrained subjects with coronary artery disease.

UNLABELLED: Exercise training improves low-density lipoprotein oxidability in untrained subjects with coronary artery disease. OBJECTIVE: To test the hypothesis that regular exercise alters low-density lipoprotein (LDL) oxidability in patients with coronary artery disease. DESIGN: Longitudinal study. SETTING: General hospital and community. PARTICIPANTS: Thirteen patients. INTERVENTIONS: Training program comprising running bouts twice weekly over 2 months. MAIN OUTCOME MEASURES: Plasma lipid profile, oxidized LDL, and rate (Ox(rate)) and amount (Ox(amount)) of LDL reaction products were measured at baseline and after 2 months of training. Brachial artery endothelium-dependent and -independent vasodilation was assessed by use of ultrasound. RESULTS: Lipid profile and oxidized LDL remained unchanged, but mean Ox(rate) and Ox(amount) +/- standard deviation were reduced from 2.5+/-1.5nmol.mgLDL(-1).min(-1) and 120.3+/-75.3nmol/mgLDL at baseline to 0.4+/-0.2nmol.mgLDL(-1).min(-1) and 21.3+/-11.4nmol/mgLDL after training (P<.05), respectively. Brachial artery vasodilation was suggested to be improved, but statistical significance was not reached in the small cohort under study. CONCLUSIONS: Aerobic training enhances the resistance of LDL to oxidation in patients with coronary artery disease, which may play a role in the favorable effects of exercise.

Intravenous iron increases labile serum iron but does not impair forearm blood flow reactivity in dialysis patients.

BACKGROUND: There are concerns about adverse vascular effects of intravenous iron by inducing oxidative stress. We therefore examined the effect of a single high dose of intravenous iron on endothelial function and biochemical markers of iron homeostasis. METHODS: In a randomized, placebo-controlled, double-blind, parallel-group study, forearm blood flow (FBF) was assessed by strain-gauge plethysmography in 38 peritoneal dialysis patients before and after a single intravenous infusion of 300 mg iron sucrose. RESULTS: Iron infusion increased total (Delta 601 microg/100 mL, CI 507, 696) and non-transferrin-bound iron (Delta 237.2 micromol/L, CI 173.6, 300.8) approximately 10-fold, as well as redox-active iron nearly five-fold (Delta 0.76 micromol/L, CI 0.54, 0.98). After iron infusion basal FBF was 59% higher than after placebo. FBF response to acetylcholine before and after iron infusion was 263 +/- 32% and 310 +/- 33%, corresponding to 304 +/- 43% and 373 +/- 29% in the placebo group, respectively. Before and after iron or placebo infusion, glyceryl-trinitrate increased resting FBF to 232 +/- 22% and 258 +/- 21% in the iron group, and to 234 +/- 18% and 270 +/- 30% in the placebo group. L-N-monomethyl-arginine decreased FBF to 70 +/- 4% and 72 +/- 3% before and after iron, and to 74 +/- 4% and 73 +/- 4% before and after placebo infusions, respectively. Despite higher basal FBF after iron infusion, absolute and relative FBF changes in response to vasoactive substances were not significantly different between iron and placebo groups. CONCLUSION: Our data suggest that 300 mg intravenous iron sucrose has a vasodilatory effect, but does not impair vascular reactivity in dialysis patients, despite a significant increase in non-transferrin-bound and redox-active iron.

History of cardiovascular disease is associated with endothelial progenitor cells in peritoneal dialysis patients.

BACKGROUND: It is unknown whether traditional cardiovascular disease risk factors influence the number of endothelial progenitor cells (EPCs) and whether numbers of EPCs correlate with endothelial function in patients with end-stage renal disease. METHODS: In a cross-sectional study of 38 peritoneal dialysis patients, we examined numbers of circulating CD34+/KDR+/CD133+ cells, CD34+ hematopoietic stem cells, and EPCs cultured from peripheral blood. We also assessed conventional cardiovascular disease risk factors, such as history of vascular disease, diabetes, hypercholesterolemia, hypertension, and smoking. We determined endothelial function by measurement of endothelium-dependent and endothelium-independent reactivity of forearm resistance arteries by using strain-gauge plethysmography. RESULTS: Numbers of EPCs cultured from peripheral blood and forearm blood flow reactivity did not differ between erythropoietin-treated peritoneal dialysis patients and healthy individuals. A history of vascular disease was associated with number of cultured EPCs, but other cardiovascular disease risk factors showed no association. Furthermore, there was no association of endothelial-dependent and endothelial-independent forearm blood flow reactivity with EPCs in peritoneal dialysis patients. CONCLUSION: In this first study of EPCs in peritoneal dialysis patients, we found an association between history of vascular disease and EPCs, but no association of EPCs with endothelial function or other cardiovascular disease risk factors.

Vasoconstrictor hyporeactivity can be reversed by antioxidants in patients with advanced alcoholic cirrhosis of the liver and ascites.

OBJECTIVE: Hyperdynamic circulation and systemic vasodilation complicate cirrhosis of the liver and are related to vasoconstrictor hyporeactivity. We investigated whether impaired vasoconstrictor responsiveness may be overcome by antioxidants in patients with decompensated alcoholic cirrhosis. DESIGN: Controlled clinical study. SETTING: University setting. PATIENTS: Nine patients with liver cirrhosis Child-Pugh grade C and nine healthy age-matched volunteers. INTERVENTIONS: Forearm blood flow responses to intra-arterial norepinephrine, angiotensin II, and the nitric oxide synthase inhibitor N-monomethyl-l-arginine were measured by strain-gauge plethysmography and compared between groups of patients. To assess the role of oxidative stress, the antioxidant vitamin C (24 mg/min) was administered locally into the brachial artery, and forearm blood flow responses were reassessed. MEASUREMENTS AND MAIN RESULTS: Plasma concentrations of vitamin C were lower in patients with cirrhosis (p < .05). In patients with cirrhosis, the reactivity to norepinephrine and angiotensin II was markedly reduced (p < .05 vs. controls). Coadministration of vitamin C completely restored the potency of vasoconstrictors to that in controls but had no effect in healthy subjects. No changes were observed in time-control experiments in cirrhosis patients (n = 3) employing vehicle coinfusion. The response to N-monomethyl-L-arginine was comparable between groups and not affected by vitamin C. CONCLUSIONS: Oxidative stress with consumption of antioxidants seems to play an important role in the development of vasoconstrictor hyporeactivity in patients with cirrhosis. Antioxidant therapy may be a promising clinical approach to restore vasoconstrictor hyporeactivity in these patients.

Naloxone does not influence cardiovascular responses to mild mental stress in postmenopausal women.

The interaction between central opioid activity, sex hormones, and the cardiovascular reactivity to stress is unknown. Twenty-eight healthy postmenopausal women, 16 without, and 12 with hormone replacement therapy (HRT) participated in this randomized, double-blind, cross-over study. The opioid receptor antagonist naloxone or placebo was administered intravenously on 2 different days and mild mental stress was induced by the Stroop Color-Word Test. Cardiovascular responses were assessed noninvasively by impedance cardiography. Stress significantly increased stroke volume, cardiac output, blood pressure, and heart rate, which was not influenced by opioid receptor blockade. Whereas naloxone increased cortisol plasma concentrations irrespective of HRT status, luteinizing hormone concentrations, which were higher in non-HRT compared with HRT women, were increased by naloxone in women with HRT only. These data suggest that the opioidergic tone of the hypothalamus-pituitary-adrenal axis persists in postmenopausal women, irrespective of HRT use, while the opioidergic tone on the hypothalamus-pituitary-gonadal axis seems to depend on an estrogenic milieu. Naloxone does not alter cardiovascular mental stress reactions in postmenopausal women independent of their hormone substitution status.