Lipoprotein Lipase Overexpression in Skeletal Muscle Attenuates Weight Regain by Potentiating Energy Expenditure

Moderate weight loss improves numerous risk factors for cardiometabolic disease; however, long-term weight loss maintenance (WLM) is often thwarted by metabolic adaptations that suppress energy expenditure and facilitate weight regain. Skeletal muscle has a prominent role in energy homeostasis; therefore, we investigated the effect of WLM and weight regain on skeletal muscle in rodents. In skeletal muscle of obesity-prone rats, WLM reduced fat oxidative capacity and downregulated genes involved in fat metabolism. Interestingly, even after weight was regained, genes involved in fat metabolism were also reduced. We then subjected mice with skeletal muscle lipoprotein lipase overexpression (mCK-hLPL), which augments fat metabolism, to WLM and weight regain and found that mCK-hLPL attenuates weight regain by potentiating energy expenditure. Irrespective of genotype, weight regain suppressed dietary fat oxidation and downregulated genes involved in fat metabolism in skeletal muscle. However, mCK-hLPL mice oxidized more fat throughout weight regain and had greater expression of genes involved in fat metabolism and lower expression of genes involved in carbohydrate metabolism during WLM and regain. In summary, these results suggest that skeletal muscle fat oxidation is reduced during WLM and regain, and therapies that improve skeletal muscle fat metabolism may attenuate rapid weight regain.     

The in vitro pharmacological profile of KR31080, a nonpeptide AT1 receptor antagonist

Summary— KR31080 (2-butyl-5-methyl-6-(1-oxopyridin-2-yl)-3-[[2'-(1H-tetrazol-5-yl) biphenyl-4-yl]methyl]-3H-imidazo[4,5-b] pyridine) is a potent inhibitor of angiotensin type 1 (AT₁) receptors in rabbit aorta and human recombinant AT₁ receptors. In the isolated rabbit thoracic aorta, KR31080 caused a nonparallel shift to the right of the concentration-response curves to angiotensin II (All) with decreased maximal response (pD'₂ = 10.1 ± 0.1), but had no effect on the contractile response induced by norepinephrine. KR31080 inhibited specific [¹²⁵I]AII binding to rabbit aortic membranes (AT, receptors) and [¹²⁵I][Sar¹, Ile⁸]AII binding to human recombinant AT₁ receptors in a concentration-dependent manner with IC₅₀ values of 0.84 ± 0.08 nM and 1.92 ± 0.15 nM, respectively, but did not inhibit specific [¹²⁵I)AII binding to bovine cerebellum membranes (ÀT₂ receptors). In the Scatchard analysis, KR31080 interacted with rabbit aortic AT₁ receptors in a competitive manner, similar to losartan. These results demonstrate that KR31080 is a potent and AT₁ selective angiotensin receptor antagonist which exerts a competitive antagonism in the [¹²⁵I]AII binding assay and insurmountable AT₁ receptor antagonism in the functional study.     

Embolisierende Thrombose bei Fehlbildung der V. cava inferior

Persistent left-sided inferior vena cava (VCI) is a rare venous anomaly, its prevalence being estimated at 0.2-0.5%. Thrombotic occlusion of a VCI has been reported in only a few of these cases. We report the case of a 24-year old woman who suffered an acute thrombosis in a left-sided VCI and recurrent pulmonary embolism. After thrombectomy the course was uneventful. The diagnostic approach and the treatment strategy are discussed with reference to the literature.     

Cotton thread method for measuring tear secretion, suitable for soft contact lens wearers (method no. 3)

Two methods of measuring lacrimation with a cotton thread and fluorescein have been described hitherto. Method 3 is intended for testing lacrimal flow in wearers of soft contact lenses. Fluorescent paper can be used to facilitate the measuring procedure. The method has been shown to be reliable in numerous control tests on subjects with normal eyes and in comparisons with the authors' methods 1 and 2. With the test, values of less than 5 mm indicate severe lacrimal deficiencies.     

Vertebroplasty and Kyphoplasty in Spinal Trauma

Abstract Kyphoplasty and vertebroplasty have become recognized procedures for the treatment of vertebral fractures, especially in patients with osteoporosis. In most cases of osteoporotic spinal vertebral fracture in elderly patients, polymethylmethacrylate (PMMA) cement is used to fill the defect and stabilize the vertebral body. The techniques of vertebroplasty and kyphoplasty differ in the possibility of realignment and reconstruction of the vertebral body and spinal column. Long-term results in terms of integration of the cement and bioreactivity of the vertebral body are still lacking; so, these procedures are still no options in the treatment of younger patients. Vertebroplasty and kyphoplasty show different success in the management of fresh traumatic spine fractures. The acute traumatic vertebral fracture has to be classified sensitively, to find the right indication for cement augmentation. Mild acute compression fractures can be treated by vertebroplasty or kyphoplasty, severe compression and burst fractures by combination of internal fixation and kyphoplasty. The indications for use of biological or osteoinductive cement in spinal fracture management must still be regarded as restricted owing to the lack of basic biomechanical research data. Such cement should not be used except in clinical studies.     

Constitutive production of interleukin-6 and tumor necrosis factor-alpha from spontaneously proliferating T cells in patients with human T-cell lymphotropic virus type-I/II.

The human T-cell lymphotropic viruses (HTLV) type I and type II are capable of inducing a variety of cellular genes, including many of the cytokines that regulate cell proliferation. To determine if the spontaneous proliferation of peripheral blood mononuclear cells from patients infected with HTLV-I and HTLV-II was related to coordinate expression of cytokines, we analyzed the levels of interleukin-1 beta (IL-1 beta), IL-2, IL-3, IL-4, IL-6, tumor necrosis factor-alpha (TNF-alpha) and interferon-tau (IFN-tau) in culture supernatants derived from spontaneously proliferating cells. Significantly elevated levels of IL-6 and TNF-alpha were present in culture supernatants from HTLV-I/II-infected individuals when compared with normal controls (P less than .01). Kinetic experiments showed that both IL-6 and TNF-alpha were elevated by day 5. None of the other cytokines (IL-1 beta, IL-2, IL-3, IL-4, and IFN-tau) were detectable in any of the culture. These data suggest that release of IL-6 and TNF-alpha may regulate lymphocyte proliferation in HTLV-I/II-infected individuals.     

Multifocal ERG with the scanning laser ophthalmoscope: query on the ideal configuration for attaining high resolution and result stability

Graefe's Archive for Clinical and Experimental Ophthalmology -