On-demand, in situ, generation of ammonium caroate (peroxymonosulfate) for the dihydroxylation of alkenes to vicinal diols

Using the dihydroxylation of alkenes as a benchmark, the reactivities of fresh and aged solutions of (NH4)2S2O8 (electrochemically generated) were compared to commercially-procured peroxydisulfate and Oxone®. The study revealed that peroxymonosulfate (Caro’s acid, PMS) is the active oxidant in such reactions. Using complementary redox colorimetry and in situ IR spectroscopy to monitor the oxidants, the competitive decomposition of peroxydisulfate in an acidic solution into PMS and H2O2 can be quantified for the first time. The new insight enabled the design and implementation of both batch and flow processes to maximise the concentration of active PMS oxidant. The utility of these oxidants for organic synthesis is demonstrated by the dihydroxylation of eight styrenes and seven alkyl alkenes, where the ammonium PMS solutions performed better than Oxone® (counterion effect). Last but not least, a non-chromatographic method for isolating and purifying the water-soluble diol product was developed

TGF-b Superfamily Cytokine MIC-1/GDF15 Is a Physiological Appetite and Body Weight Regulator

The TGF-b superfamily cytokine MIC-1/GDF15 circulates in all humans and when overproduced in cancer leads to anorexia/cachexia, by direct action on brain feeding centres. In these studies we have examined the role of physiologically relevant levels of MIC-1/GDF15 in the regulation of appetite, body weight and basal metabolic rate. MIC-1/GDF15 gene knockout mice (MIC-1−/−) weighed more and had increased adiposity, which was associated with increased spontaneous food intake. Female MIC-1−/− mice exhibited some additional alterations in reduced basal energy expenditure and physical activity, possibly owing to the associated decrease in total lean mass. Further, infusion of human recombinant MIC-1/GDF15 sufficient to raise serum levels in MIC-1−/− mice to within the normal human range reduced body weight and food intake. Taken together, our findings suggest that MIC-1/GDF15 is involved in the physiological regulation of appetite and energy storage

X-ray free electron laser heating of water and gold at high static pressure

The study of water at high pressure and temperature is essential for understanding planetary interiors but is hampered by the high reactivity of water at extreme conditions. Here, indirect X-ray laser heating of water in a diamond anvil cell is realized via a gold absorber, showing no evidence of reactivity

Alterations in antioxidant enzyme activities in the eyes, aorta and kidneys of diabetic rats relevant to the onset of oxidative stress

Profound changes in antioxidant enzyme activities were observed in a number of vascular tissues during the development of streptozotocin-induced diabetes in rats. In the eyes, there was an increase in superoxide dismutase activity at week 4 of diabetes. However, no difference in superoxide dismutase activity was observed between the control and diabetic animals at week 8. On the other hand, the diabetic state did not seem to affect the catalase activity in the eyes. There was a generalized increase in catalase activity of the eyes from week 4 to week 8 irrespective of the diabetic state. For glutathione peroxidase in the eyes, a decreased activity was observed in the diabetic animals at week 8, but not in week 4. A different pattern of enzyme activity changes was observed in the aorta where an increase in superoxide dismutase activity was observed in the diabetic group at week 4 but not in week 8. On the other hand, an increase in catalase activity was observed only at week 8 but not at week 4. Whereas there was no observed difference between the control and diabetic animals in glutathione peroxidase activity in the aorta, except for a generalized decrease from week 4 to week 8 in both groups of animals. In big contrast to the eyes and aorta where an increase in superoxide dismutase activity was observed at week 4 of diabetes, no change in kidney superoxide dismutase activity was noted at week 4 and a decrease was observed at week 8. A similar pattern of enzyme activity changes was observed for glutathione peroxidase in the kidneys. The catalase activity in the kidneys was not affected at all by the diabetic state at both week 4 and week 8. These results clearly demonstrate the active involvement of these antioxidant enzymes during the development of diabetes, and could be rationalized by the differential response of the tissues towards the different extent of oxidative stress imposed by the diabetic state on the different tissues.link_to_subscribed_fulltex

Anorexia/cachexia of chronic diseases: a role for the TGF-beta family cytokine MIC-1/GDF15

Anorexia/cachexia is a common and currently mostly untreatable complication of advanced cancer. It is also a feature of a number of chronic diseases and can also occur as part of the normal ageing process. Over recent years, two different, but sometimes overlapping, processes have been identified to mediate anorexia/cachexia: those that act primarily on muscle reducing its mass and function, and processes that decrease nutrition leading to loss of both fat and muscle. In the case of at least some cancers, the latter process is sometimes driven by marked overexpression of macrophage inhibitory cytokine-1/growth differentiation factor 15 (MIC-1/GDF15). MIC-1/GDF15 is a transforming growth factor beta (TGF-beta) family cytokine that is found in the serum of all normal individuals at an average concentration of about 0.6 ng/ml. Its increased expression in both cancers and other diseases can result in 10-100-fold or more elevation of its serum levels. In experimental animals, serum MIC-1/GDF15 levels at the lower end of this range induce anorexia by direct actions of the circulating cytokine on feeding centres in the brain. Mice with tumours overexpressing MIC-1/GDF15 display decreased food intake, loss of lean and fat mass and cachexia. That this process also mediates anorexia/cachexia in humans is suggested by the fact that there is a direct correlation between the degree of serum MIC-1/GDF15 elevation and the amount of cancer-related weight loss, the first such relationship demonstrated. Further, in experimental animals, weight loss can be reversed by neutralisation of tumour-produced MIC-1/GDF15 with a specific monoclonal antibody, suggesting the possibility of effective therapy of patients with the devastating complication of anorexia/cachexia

The anorectic actions of the TGFβ cytokine MIC-1/GDF15 require an intact brainstem area postrema and nucleus of the solitary tract

Macrophage inhibitory cytokine-1 (MIC-1/GDF15) modulates food intake and body weight under physiological and pathological conditions by acting on the hypothalamus and brainstem. When overexpressed in disease, such as in advanced cancer, elevated serum MIC-1/GDF15 levels lead to an anorexia/cachexia syndrome. To gain a better understanding of its actions in the brainstem we studied MIC-1/GDF15 induced neuronal activation identified by induction of Fos protein. Intraperitoneal injection of human MIC-1/GDF15 in mice activated brainstem neurons in the area postrema (AP) and the medial (m) portion of the nucleus of the solitary tract (NTS), which did not stain with tyrosine hydroxylase (TH). To determine the importance of these brainstem nuclei in the anorexigenic effect of MIC-1/GDF15, we ablated the AP alone or the AP and the NTS. The latter combined lesion completely reversed the anorexigenic effects of MIC-1/GDF15. Altogether, this study identified neurons in the AP and/or NTS, as being critical for the regulation of food intake and body weight by MIC-1/GDF15. © 2014 Tsai et al