Sturzrisiko und Frakturhäufigkeit bei postmenopausalen Patientinnnen mit Rheumatoider Arthritis und erniedrigter Knochendichte

Die Dissertation befasst sich mit dem Sturzrisiko und der Frakturhäufigkeit bei postmenopausalen Patientinnen mit Rheumatoider Arthritis und erniedrigter Knochendichte. Hierbei konnten der erhöhte BMI und Stürze in der Vergangenheit als bedeutendste Einflussfaktoren auf das Sturzrisiko der Patientinnen identifiziert werden. Das Frakturrisiko ist auf Grund der reduzierten Knochendichte und des Struzrisikos in unserem Patientenkollektiv erhöht. Die angewandten Testmethoden zur Einschätzung des Sturzrisikos können gleichzeitig als Trainingseinheit zur Verbesserung der Defizite genutzt werden

Liver X Receptor Agonist AZ876 Induces Beneficial Endogenous Cardiac Lipid Reprogramming and Protects Against Isoproterenol‐Induced Cardiac Damage

Background: It is known that dietary intake of polyunsaturated fatty acids may improve cardiac function. However, relatively high daily doses are required to achieve sufficient cardiac concentrations of beneficial omega-3 fatty acids. The liver X receptor (LXR) is a nuclear hormone receptor and a crucial regulator of lipid homeostasis in mammals. LXR activation has been shown to endogenously reprogram cellular lipid profiles toward increased polyunsaturated fatty acids levels. Here we studied whether LXR lipid reprogramming occurs in cardiac tissue and exerts cardioprotective actions. Methods and Results: Male 129SV mice were treated with the LXR agonist AZ876 (20 mu mol/kg per day) for 11 days. From day 6, the mice were injected with the nonselective beta-agonist isoproterenol for 4 consecutive days to induce diastolic dysfunction and subendocardial fibrosis while maintaining systolic function. Treatment with isoproterenol led to a marked impairment of global longitudinal strain and the E/e' ratio of transmitral flow to mitral annular velocity, which were both significantly improved by the LXR agonist. Histological examination showed a significant reduction in isoproterenol-induced subendocardial fibrosis by AZ876. Analysis of the cardiac lipid composition by liquid chromatography-high resolution mass spectrometry revealed a significant increase in cardiac polyunsaturated fatty acids levels and a significant reduction in saturated fatty acids by AZ876. Conclusions: The present study provides evidence that the LXR agonist AZ876 prevents subendocardial damage, improves global longitudinal strain and E/e' in a mouse model of isoproterenol-induced cardiac damage, accompanied by an upregulation of cardiac polyunsaturated fatty acids levels. Cardiac LXR activation and beneficial endogenous cardiac lipid reprogramming may provide a new therapeutic strategy in cardiac disease with diastolic dysfunction

Beneficial effects of exercise on offspring obesity and insulin resistance are reduced by maternal high-fat diet

SCOPE: We investigated the long-term effects of maternal high-fat consumption and post-weaning exercise on offspring obesity susceptibility and insulin resistance. METHODS: C57BL/6J dams were fed either a high-fat (HFD, 40% kcal fat) or low-fat (LFD, 10% kcal fat) semi-synthetic diet during pregnancy and lactation. After weaning, male offspring of both maternal diet groups (mLFD; mHFD) received a LFD. At week 7, half of the mice got access to a running wheel (+RW) as voluntary exercise training. To induce obesity, all offspring groups (mLFD +/-RW and mHFD +/-RW) received HFD from week 15 until week 25. RESULTS: Compared to mLFD, mHFD offspring were more prone to HFD-induced body fat gain and exhibited an increased liver mass which was not due to increased hepatic triglyceride levels. RW improved the endurance capacity in mLFD, but not in mHFD offspring. Additionally, mHFD offspring +RW exhibited higher plasma insulin levels during glucose tolerance test and an elevated basal pancreatic insulin production compared to mLFD offspring. CONCLUSION: Taken together, maternal HFD reduced offspring responsiveness to the beneficial effects of voluntary exercise training regarding the improvement of endurance capacity, reduction of fat mass gain, and amelioration of HFD-induced insulin resistance

Correction: Beneficial effects of exercise on offspring obesity and insulin resistance are reduced by maternal high-fat diet.

[This corrects the article DOI: 10.1371/journal.pone.0173076.]

Impact of maternal high-fat feeding on offspring training efficiency and fiber type composition.

<p>Maternal low-fat diet (mLFD) or maternal high-fat diet (mHFD) offspring were fed a LFD after weaning throughout an age of 15 wks. Afterwards they received a HFD for 10 wks. Half of each group had access to a running wheel (RW) for voluntary training. (A) endurance capacity at wk 7, (B) training efficiency and (C/D) gene expression of myosin heave chain (Mhc) isoforms in M. quadriceps (C) and M. soleus (D). For Mhc gene expression, the Con group (mLFD-RW LFD) was set to 1. Data are mean ±SE; (A) n = 43-53; (B/C) n = 11-15; (C/D) n = 5-8. Data were compared by two-way ANOVA (Bonferroni post hoc test); # indicates significant differences between the maternal diets (mLFD and mHFD), whereas * indicates significant RW effects (-RW vs. +RW).</p

Experimental study design.

<p>Dams were either fed a low-fat (LFD) or a high-fat diet (HFD) before and throughout pregnancy and lactation. After weaning, male offspring received LFD until an age of 15 wks. At an age of 15 wks, mice received HFD for 10 wks. Half of each group got access to a running wheel (RW) as voluntary exercise training. As a control (baseline) group (Con), mLFD offspring without RW access were fed LFD during the whole experiment. Body composition and treadmill exercise capacity were measured in wk 7, 15, and 25. A four-hour oral glucose tolerance test (oGTT) was performed in wk 22 and indirect calorimetry (IC) was performed in wk 24.</p

Impact of maternal high-fat diet intake on offspring HFD-induced insulin resistance.

<p>Maternal low-fat diet (mLFD) or maternal high-fat diet (mHFD) offspring were fed a LFD after weaning throughout an age of 15 wks. Afterwards they received a HFD for 10 wks. Half of each group had access to a running wheel (RW) for voluntary training. (A) glucose tolerance, (B) insulin sensitivity, (C) pancreas insulin content and (D) basal blood glucose concentration. The dotted line in C/D indicates the level of the Con group (mLFD-RW LFD). Data are mean ±SE (A) n = 8-15; (B) n = 10-15; (C) n = 5-6; (D) n = 6-12. Data were compared by two-way ANOVA (Bonferroni post hoc test). # indicates significant differences between the maternal diets (mLFD and mHFD), whereas * indicates significant RW effects (-RW vs. +RW).</p

Impact of maternal high-fat intake on the offspring’s liver parameters.

<p>Maternal low-fat diet (mLFD) or maternal high-fat diet (mHFD) offspring were fed LFD after weaning throughout an age of 15 wks. Afterwards they received HFD for 10 wks. Half of each group had access to a running wheel (RW) for voluntary training. (A) offspring liver weight, (B/C) hepatic triglyceride concentration and its correlation with liver weight, (D/E) hepatic glycogen content and the respective correlation with liver weight. The dotted line in A/B/D indicates the level of the Con group (mLFD-RW LFD). Data are expressed as median with interquartile range (A/B) or mean +SE (D), (A) n = 10-15; (B) n = 6-12; (D) n = 4-11. Data were analyzed by Kruskal Wallis (Dunn´s test) or two-way ANOVA (Bonferroni post hoc test). (C/E) Spearman correlation analyses were performed with -RW animals.</p

Odorant stimulation of secretory and neural processes in the salamander olfactory mucosa

Summary1.Topical application of the odorants guaiacol (10−3 mol/l, 1–30 min) and 2-isobutyl-3-methoxypyrazine (IBMP, 10−5–10−3 mol/l, 15 min) caused time- and concentration-dependent reductions in the secretory granule content of acinar cells of the superficial Bowman\u27s glands (sBG) and moderate to extensive vacuolation in acinar cells of sBG and deep olfactory glands (dG). 2.Topical application of 9.8 mg/ml scopolamine 10 min before 10−4 mol/l IBMP significantly reduced the amount of secretory granule depletion from sBG compared to that seen with IBMP alone and resulted in less extensive vacuolation in sBG and dG acinar cells. The i.p. injection of 42 mg/kg propranolol 10 min before topical application of 10−4 mol/l IBMP had no effect on the action of IBMP. 3.Guaiacol and IBMP also had time- and concentration-dependent effects on the secretory activity of sustentacular cells in the olfactory epithelium. The protrusion of secretory material into the mucociliary matrix that covers the epithelial surface and vacuolation within the secretory material resulted from odorant application. Scopolamine and propranolol had no effects on the action of IBMP on sustentacular cell secretory activity. 4.When applied in the vapor phase, guaiacol elicited action potentials recorded from individual olfactory receptor neurons; the impulse frequency was concentration-dependent and showed tonic and phasic components when the duration of stimulation was varied. Low to moderate concentrations of IBMP delivered in the vapor phase evoked monophasic negative slow voltage transients recorded from the surface of the olfactory mucosa. The amplitudes of these transients increased with increasing stimulus concentrations. Higher concentrations or longer stimulus durations evoked longer-latency positive-voltage generating processes and negative afterpotentials. The properties of the electrophysiological responses to both odorants were characteristic of responses evoked by a wide variety of ‘typical’ odorants