ABSTRACT
Adult bone regeneration is orchestrated by the precise actions of osteoprogenitor cells (OPCs). However, the mechanisms by which OPC proliferation and differentiation are linked and thereby regulated are yet to be defined. Here, we present evidence that during intramembranous bone formation OPC proliferation is controlled by Notch signaling, while differentiation is initiated by activation of canonical Wnt signaling. The temporospatial separation of Notch and Wnt signal activation during the early stages of bone regeneration suggests crosstalk between the two pathways. In vitro and in vivo manipulation of the two essential pathways demonstrate that Wnt activation leads to initiation of osteogenic differentiation and at the same time inhibits Notch signaling, which results in termination of the proliferative phase. Here, we establish canonical Wnt signaling as a key regulator that facilitates the crosstalk between OPC proliferation and differentiation during intramembranous, primary bone healing.
ABSTRACT
PURPOSE: The primary aim of this research was to evaluate the effect of acute norepinephrine (NE) infusion on the exercise oxygen utilization in heart failure patients as compared with healthy adults. METHODS: Eleven healthy adults and 10 patients with NYHA class II-III heart failure (ejection fraction <40%) who were not on beta-blocker therapy underwent steady state exercise under placebo or NE infusion conditions, followed by maximal ramp exercise testing. Oxygen utilization, hemodynamic responses, and serum lactate NE levels were evaluated. RESULTS: The hemodynamic effects of NE were evident in both groups with statistically significant increases in blood pressure and concomitant decreases in heart rates. Lactate levels were higher in heart failure subjects under all conditions and steady state exercise increased levels by 24% (P = 0.04). NE infusion increased lactate levels by a nonsignificant 24% (P = 0.19). NE infusion tended to increase oxygen consumption (VO2) at the end of steady state exercise in CHF subjects (4% change; P = 0.06). Compared with healthy adults, NE infusion significantly impaired (increased) the gross VO2/W relationship in heart failure subjects (P = 0.037). There was also a modest trend for a worsening (decrease) in net efficiency after NE infusion in CHF subjects. There were no significant adverse effects of low-dose NE infusion in either group. CONCLUSIONS: We conclude that 1) acute low-dose NE infusion impairs the oxygen utilization in stable heart failure patients but not in healthy adults. This may help to explain the exercise intolerance that accompanies congestive heart failure. 2) Acute infusion of low-dose NE infusion is safe and well tolerated in both healthy adults and compensated heart failure patients.
Subject(s)
Exercise/physiology , Heart Failure/physiopathology , Norepinephrine/pharmacology , Oxygen Consumption/drug effects , Sympathomimetics/pharmacology , Ventricular Dysfunction, Left/physiopathology , Adult , Exercise Test , Exercise Tolerance/physiology , Female , Hemodynamics , Humans , Infusions, Intravenous , Male , Middle Aged , Norepinephrine/administration & dosage , Prognosis , Sympathomimetics/administration & dosageSubject(s)
Aortic Dissection/therapy , Coronary Aneurysm/therapy , Stents , Adult , Aortic Dissection/diagnosis , Aortic Dissection/diagnostic imaging , Cardiac Catheterization , Coronary Aneurysm/diagnosis , Coronary Aneurysm/diagnostic imaging , Electrocardiography , Emergency Treatment , Female , Fibrinolytic Agents/therapeutic use , Fluoroscopy , Humans , Time FactorsABSTRACT
Benign nocturnal leg cramps are a relatively common and bothersome complaint, particularly among the elderly. Careful history taking and physical examination can exclude the majority of disorders in the differential diagnosis. Mechanical treatment of an acute muscle cramp involves stretching of the affected muscle. Prophylaxis includes both mechanical and pharmacologic measures. The efficacy of quinine sulfate has been supported in the majority of well-designed studies, but its use is controversial, and the FDA has banned over-the-counter quinine-based products used for leg cramps. Potentially fatal hypersensitivity reactions and thrombocytopenia can occur with use of quinine.
Subject(s)
Leg , Muscle Cramp/drug therapy , Quinine/therapeutic use , Humans , Muscle Cramp/diagnosis , Muscle Cramp/prevention & controlABSTRACT
Despite public health efforts, heart disease remains a leading cause of death and disease in the United States. There is sufficient evidence to justify the inclusion of regular exercise in efforts to reduce overall coronary heart disease (CHD) morbidity and mortality. This paper reviews the supportive evidence for this stance as well as the role of exercise in managing the major CHD risk factors of atherogenic serum lipids, hypertension, and obesity. Recognition of exercise as a lifestyle behavior is addressed and recommendations for prescribing exercise for adults interested in preventing CHD are presented.
