Electrochemically Induced RAFT Polymerization of Thermoresponsive Hydrogel Films: Impact on Film Thickness and Surface Morphology

Thin hydrogel films of the thermoresponsive polymer poly(N‐isopropylacrylamide) (pNIPAm) were prepared by electrochemically triggered reversible addition‐fragmentation chain transfer (RAFT) polymerization. Two different RAFT agents were employed, which work in either acidic or basic solution. In both cases, addition of RAFT agents had an influence on the thickness and the surface morphology of the films. At low concentration, the polymerization efficiency increased. At high concentration, the efficiency decreased at acidic pH, while it remained constant under basic conditions. Neither RAFT agent displayed electrochemical activity on its own, but they did modify the electrochemical behavior of the initiator. The addition of RAFT agent strongly enhances the homogeneity of the hydrogel surfaces, which presumably is due to a reduced amount of microgel formation.

     

Ernährungsmedizinische Optionen bei Adipositas und metabolischem Syndrom

Long-term stabilization of weight after a decrease in weight makes sense together with a fat-reduced, fiber-rich, well-balanced diet. "Little sins" depending on the patient's preferences are acceptable. A complete day-food report is very important.A short-term decrease in weight can be achieved by a diet rich in fat. For a long-term stabilization of weight one should switch to a fat-reduced, well-balanced diet, because there are no data from long-lasting studies of "low-carb diets".During intervention all diets show a positive effect. If, however, the decreased consumption of energy by reduced weight is not considered in the diet, a reincrease in weight will result. The regulation of satiety and hunger is mainly determined by the volume of nutrition and less by nutritive substances. So it is not surprising that food with a lower energy density seems to be advantageous.To achieve long-term positive results, a good patient compliance combined with daily physical activity is important.     

Benfotiamine prevents macro- and microvascular endothelial dysfunction and oxidative stress following a meal rich in advanced glycation end products in individuals with type 2 diabetes

OBJECTIVE: Diabetes is characterized by marked postprandial endothelial dysfunction induced by hyperglycemia, hypertriglyceridemia, advanced glycation end products (AGEs), and dicarbonyls (e.g., methylglyoxal [MG]). In vitro hyperglycemia-induced MG formation and endothelial dysfunction could be blocked by benfotiamine, but in vivo effects of benfotiamine on postprandial endothelial dysfunction and MG synthesis have not been investigated in humans until now. RESEARCH DESIGN AND METHODS: Thirteen people with type 2 diabetes were given a heat-processed test meal with a high AGE content (HAGE; 15.100 AGE kU, 580 kcal, 54 g protein, 17 g lipids, and 48 g carbohydrates) before and after a 3-day therapy with benfotiamine (1,050 mg/day). Macrovascular flow-mediated dilatation (FMD) and microvascular reactive hyperemia, along with serum markers of endothelial disfunction (E-selectin, vascular cell adhesion molecule-1, and intracellular adhesion molecule-1), oxidative stress, AGE, and MG were measured during both test meal days after an overnight fast and then at 2, 4, and 6 h postprandially. RESULTS: The HAGE induced a maximum reactive hyperemia decrease of -60.0% after 2 h and a maximum FMD impairment of -35.1% after 4 h, without affecting endothelium-independent vasodilatation. The effects of HAGE on both FMD and reactive hyperemia were completely prevented by benfotiamine. Serum markers of endothelial dysfunction and oxidative stress, as well as AGE, increased after HAGE. These effects were significantly reduced by benfotiamine. CONCLUSIONS: Our study confirms micro- and macrovascular endothelial dysfunction accompanied by increased oxidative stress following a real-life, heat-processed, AGE-rich meal in individuals with type 2 diabetes and suggests benfotiamine as a potential treatment.     

Breast cancer risk during HRT: influence of estradiol metabolites on breast cancer and endothelial cell proliferation

OBJECTIVES: Long-term hormone replacement therapy is associated with an increased breast cancer risk. Evidence is accumulating that estradiol metabolites are involved in carcinogenesis. These metabolites may have proliferating and anti-proliferative properties. We have investigated the effect of 14 metabolites on the proliferation of human breast cancer cells and on the proliferation of human vascular endothelial cells. METHODS: As cell model, human umbilical vein endothelial cells (HUVEC) and the human breast cancer cell line MCF-7 were used. The relationship between dosage and effect was tested over the pharmacological concentration range of 10(-8) to 10(-5) M. RESULTS: In HUVECs, all of 10 A-ring metabolites tested stimulated the growth of the endothelial cells at the lower concentrations. At the highest concentration, some A-ring metabolites caused significant inhibitions. The D-ring metabolites showed no marked effects compared to the A-ring metabolites. In MCF-7 cells also, nearly all A-ring metabolites demonstrated a biphasic reaction behaviour on cell proliferation. For the D-ring metabolites, this biphasic pattern was only found for 16 alpha-hydroxyestrone, but the inhibitory effect of this metabolite was weak. CONCLUSION: These results indicate that certain endogenous estradiol metabolites are able to stimulate breast cancer cell proliferation, and others may be suitable for breast cancer treatment when used in high dosages, since they inhibit cancer cell growth as well as neoangiogensis. This may be of special importance for therapy, since some of these metabolites are virtually devoid of any oestrogenic activity.     

Repeated Stress Dysregulates κ-Opioid Receptor Signaling in the Dorsal Raphe through a p38α MAPK-Dependent Mechanism

Repeated stress releases dynorphins and causes subsequent activation of κ-opioid receptors (KORs) in limbic brain regions. The serotonergic dorsal raphe nucleus (DRN) has previously been found to be an important site of action for the dysphoric effects of dynorphin-κ-opioid receptor system activation during stress-evoked behaviors, and KOR-induced activation of p38α mitogen-activated protein kinase (MAPK) in serotonergic neurons was found to be a critical mediator of the aversive properties of stress. Yet, how dynorphins and KORs functionally regulate the excitability of serotonergic DRN neurons both in adaptive and pathological stress states is poorly understood. Here we report that acute KOR activation by the selective agonist U69,593 [(+)-(5α,7α,8β)-N-methyl-N-[7-(1-pyrrolidinyl)-1-oxaspiro[4.5]dec-8-yl]benzeneacetamide] inhibits serotonergic neuronal excitability within the DRN through both presynaptic inhibition of excitatory synaptic transmission and postsynaptic activation of G-protein-gated inwardly rectifying potassium channels (GIRKs) electrophysiologically recorded in brain slices. C57BL/6 mice subjected to repeated swim, stress sessions had significantly reduced KOR-mediated GIRK currents recorded in serotonergic neurons in DRN postsynaptically, without significantly affecting presynaptic KOR-mediated regulation of excitatory transmission. This effect was blocked by genetic excision of p38α MAPK selectively from serotonergic neurons. An increase in phospho-immunoreactivity suggests that this functional dysregulation may be a consequence of tyrosine phosphorylation of GIRK (K(IR)3.1) channels. These data elucidate a mechanism for stress-induced dysregulation of the excitability of neurons in the DRN and identify a functional target of stress-induced p38α MAPK activation that may underlie some of the negative effects of pathological stress exposure.