Chlorido(pentane-2,4-dionato-κ2 O,O′)(1,10-phenanthroline-κ2 N,N′)copper(II)

The CuII atom in the title compound, [Cu(C5H7O2)Cl(C12H8N2)], shows a distorted square-planar coordination; the chelating N and O atoms occupy the basal sites and the Cl atom the apical site. The square-pyramidal character along the Berry D 3h–C 4v pseudorotation pathway is 92%

Micro-CT imaging reveals<i> Mekk3 </i>heterozygosity prevents cerebral cavernous malformations in <i>Ccm2</i>-deficient mice

Mutations in CCM1 (aka KRIT1), CCM2, or CCM3 (aka PDCD10) gene cause cerebral cavernous malformation in humans. Mouse models of CCM disease have been established by deleting Ccm genes in postnatal animals. These mouse models provide invaluable tools to investigate molecular mechanism and therapeutic approaches for CCM disease. However, the full value of these animal models is limited by the lack of an accurate and quantitative method to assess lesion burden and progression. In the present study we have established a refined and detailed contrast enhanced X-ray micro-CT method to measure CCM lesion burden in mouse brains. As this study utilized a voxel dimension of 9.5μm (leading to a minimum feature size of approximately 25μm), it is therefore sufficient to measure CCM lesion volume and number globally and accurately, and provide high-resolution 3-D mapping of CCM lesions in mouse brains. Using this method, we found loss of Ccm1 or Ccm2 in neonatal endothelium confers CCM lesions in the mouse hindbrain with similar total volume and number. This quantitative approach also demonstrated a rescue of CCM lesions with simultaneous deletion of one allele of Mekk3. This method would enhance the value of the established mouse models to study the molecular basis and potential therapies for CCM and other cerebrovascular diseases

Deletion of Wntless in myeloid cells exacerbates liver fibrosis and the ductular reaction in chronic liver injury

Background: Macrophages play critical roles in liver regeneration, fibrosis development and resolution. They are among the first responders to liver injury and are implicated in orchestrating the fibrogenic response via multiple mechanisms. Macrophages are also intimately associated with the activated hepatic progenitor cell (HPC) niche or ductular reaction that develops in parallel with fibrosis. Among the many macrophage-derived mediators implicated in liver disease progression, a key role for macrophage-derived Wnt proteins in driving pro-regenerative HPC activation towards a hepatocellular fate has been suggested. Wnt proteins, in general, however, have been associated with both pro-and anti-fibrogenic activities in the liver and other organs. We investigated the role of macrophage-derived Wnt proteins in fibrogenesis and HPC activation in murine models of chronic liver disease by conditionally deleting Wntless expression, which encodes a chaperone essential for Wnt protein secretion, in LysM-Cre-expressing myeloid cells (LysM-Wls mice)

Tocotrienols reverse cardiovascular, metabolic and liver changes in high carbohydrate, high fat diet-fed rats

Tocotrienols have been reported to improve lipid profiles, reduce atherosclerotic lesions, decrease blood glucose and glycated haemoglobin concentrations, normalise blood pressure in vivo and inhibit adipogenesis in vitro, yet their role in the metabolic syndrome has not been investigated. In this study, we investigated the effects of palm tocotrienol-rich fraction (TRF) on high carbohydrate, high fat diet-induced metabolic, cardiovascular and liver dysfunction in rats. Rats fed a high carbohydrate, high fat diet for 16 weeks developed abdominal obesity, hypertension, impaired glucose and insulin tolerance with increased ventricular stiffness, lower systolic function and reduced liver function. TRF treatment improved ventricular function, attenuated cardiac stiffness and hypertension, and improved glucose and insulin tolerance, with reduced left ventricular collagen deposition and inflammatory cell infiltration. TRF improved liver structure and function with reduced plasma liver enzymes, inflammatory cell infiltration, fat vacuoles and balloon hepatocytes. TRF reduced plasma free fatty acid and triglyceride concentrations but only omental fat deposition was decreased in the abdomen. These results suggest that tocotrienols protect the heart and liver, and improve plasma glucose and lipid profiles with minimal changes in abdominal obesity in this model of human metabolic syndrome

Tocotrienols as possible treatments for obesity

Obesity is excessive fat storage, usually defined in humans by the ratio of body mass to height (body mass index or BMI). In European populations, overweight is defined as BMI values >25 and obesity as values >30. In Asian populations, these cutoffs are usually decreased to 23 for overweight and 27 for obesity, since, at a given BMI, Asians have an increased percentage of body fat compared to Europeans (Deurenberg-Yap et al., 2000; WHO Expert Consultation, 2004). The incidence of obesity is increasing worldwide. The World Health Organization (WHO) estimates that more than 1 billion adults worldwide are overweight; of these, at least 300 million are obese (Ahima and Flier, 2000). In Australia, the proportion of overweight and obese adults increased from 41% in 1995 to 49% in 2004-2005 and about 61% in 2007-2008. In 2008, 42.2% of adult males were overweight and 25.4% were obese while the comparable gures for females were 31.1% and 23.7%, respectively (Australian Institute of Health and Welfare, 2008, 2010; Australian Bureau of Statistics, 2011a). This mirrors changes in other developed countries. In 2007-2008, the prevalence of obesity was 32.2% among adult men and 35.5% among adult women in the United States (Flegal et al., 2010). In the United Kingdom, the prevalence of obesity increased markedly from 13.2% of men in 1993 to 26.2% in 2010 and from 16.4% of women in 1993 to 26.2% in 2010 while the proportion of overweight was stable at 40% for men and 30% for women (The NHS Information Centre, Lifestyles Statistics, 2012)). In Sweden, this figure increased from 35% in 1980 to 52% in 2007 in adult men and from 27% to 36% in adult women (Johansson, 2010). The problem is less marked in developing countries but these societies are also showing an increasing incidence of overweight and obesity. In the decade from 1996 to 2006, the prevalence of overweight adults in Malaysia increased from 20.7% to 29.1% with an even larger proportional increase in obesity from 5.5% to 14.0% (Khambalia and Seen, 2010). In China, the prevalence of overweight and obesity (BMI ≤ 25.0 kg/m) among adults aged 18 years or older increased from 14.6% in 1992 to 21.8% in 2002, and the prevalence among adults aged from 18 to 44 years almost tripled (Wang et al., 2006). In populations from industrial areas in India, 30.9% of men and 32.8% of women showed abdominal obesity in 2002-2003 (Reddy et al., 2006)

Nutrapharmacology of tocotrienols for metabolic syndrome

Metabolic syndrome is defined as a set of health risk factors that are associated with an increased chance of cardiovascular diseases and type 2 diabetes. These include abdominal obesity, hyperglycemia, impaired glucose tolerance, dyslipidemia, and hypertension. Interventions in metabolic syndrome include lifestyle interventions such as a healthy diet using functional foods together with increased physical activity to induce weight loss as the first aim of treatment. Nutraceuticals such as tocotrienols and tocopherols as members of the vitamin E family may be more targeted interventions. This review evaluates the effects of tocotrienols on the risk factors of metabolic syndrome using data from human, animal and in vitro studies. Tocotrienols improved lipid profiles and reduced atherosclerotic lesions, decreased blood glucose and glycated hemoglobin concentrations, normalized blood pressure, and inhibited adipogenesis. The differences in responses between tocopherols and tocotrienols in preventing obesity, diabetes, hypertension, atherosclerosis, ischemia, and inflammation suggest that different receptors or signaling mechanisms may be involved

Development of a depth meter with automatic temperature compensation

85 p.A method to compensate the temperature effect on twin wire resistance probe depth metfiod was presented. Both analog and digital circuits were designed, fabricated, and tested. The error in measurement due to temperature effect could be greatiy reduced.RP-M-24-8

Caffeine attenuates metabolic syndrome in diet-induced obese rats

Objective: Caffeine is a constituent of many non-alcoholic beverages. Pharmacological actions of caffeine include the antagonism of adenosine receptors and the inhibition of phosphodiesterase activity. The A1 adenosine receptors present on adipocytes are involved in the control of fatty acid uptake and lipolysis. In this study, the effects of caffeine were characterized in a diet-induced metabolic syndrome in rats. Methods: Rats were given a high-carbohydrate, high-fat diet (mainly containing fructose and beef tallow) for 16 wk. The control rats were given a corn starch diet. Treatment groups were given caffeine 0.5 g/kg of food for the last 8 wk of the 16-wk protocol. The structure and function of the heart and the liver were investigated in addition to the metabolic parameters including the plasma lipid components. Results: The high-carbohydrate, high-fat diet induced symptoms of metabolic syndrome, including obesity, dyslipidemia, impaired glucose tolerance, decreased insulin sensitivity, and increased systolic blood pressure, associated with the development of cardiovascular remodeling and nonalcoholic steatohepatitis. The treatment with caffeine in the rats fed the high-carbohydrate, high-fat diet decreased body fat and systolic blood pressure, improved glucose tolerance and insulin sensitivity, and attenuated cardiovascular and hepatic abnormalities, although the plasma lipid concentrations were further increased. Conclusion: Decreased total body fat, concurrent with increased plasma lipid concentrations, reflects the lipolytic effects of caffeine in adipocytes, likely owing to the caffeine antagonism of A1 adenosine receptors on adipocytes

Anti-inflammatory γ- and δ-tocotrienols improve cardiovascular, liver and metabolic function in diet-induced obese rats

Purpose This study tested the hypothesis that γ- and δ-tocotrienols are more effective than α-tocotrienol and α-tocopherol in attenuating the signs of diet-induced metabolic syndrome in rats. Methods Five groups of rats were fed a corn starch-rich (C) diet containing 68%carbohydrates as polysaccharides, while the other five groups were fed a diet (H) high in simple carbohydrates (fructose and sucrose in food, 25 % fructose in drinking water, total 68 %) and fats (beef tallow, total 24 %) for 16 weeks. Separate groups from each diet were supplemented with either α-, γ-, δ-tocotrienol or α-tocopherol (85 mg/kg/day) for the final 8 of the 16 weeks. Results H rats developed visceral obesity, hypertension, insulin resistance, cardiovascular remodelling and fatty liver. α-Tocopherol, α-, γ- and δ-tocotrienols reduced collagen deposition and inflammatory cell infiltration in the heart. Only γ- and δ-tocotrienols improved cardiovascular function and normalised systolic blood pressure compared to H rats. Further, δ-tocotrienol improved glucose tolerance, insulin sensitivity, lipid profile and abdominal adiposity. In the liver, these interventions reduced lipid accumulation, inflammatory infiltrates and plasma liver enzyme activities. Tocotrienols were measured in heart, liver and adipose tissue showing that chronic oral dosage delivered tocotrienols to these organs despite low or no detection of tocotrienols in plasma. Conclusion In rats, δ-tocotrienol improved inflammation, heart structure and function, and liver structure and function, while γ-tocotrienol produced more modest improvements, with minimal changes with α-tocotrienol and α-tocopherol. The most important mechanism of action is likely to be reduction in organ inflammation