Dietary copper in the physiology of the microcirculation

Dietary copper has long been known to be essential for cardiovascular homeostasis. However, the role of copper and cuproenzymes in the normal control of vascular physiology is not well understood. Most studies in the cardiovascular system have focused on copper deficiency-induced defects in the heart or large vessels. Recently, attention has also focused on the effects of copper deficiency in the microcirculation or the small blood vessels that control blood flow, nutrient and waste exchange, and peripheral vascular resistance. Studies in the microcirculation demonstrate that copper is important in mechanisms of macromolecular leakage, platelet-endothelial interactions and vascular smooth muscle reactivity. There is a significantly greater leakage of proteins from postcapillary venules in copper-deficient rats in response to mast cell-released histamine. This response appears to be the result of increased numbers of mast cells and thereby increased available histamine. Copper deficiency also causes an inhibition of in vivo thrombogenesis, which appears to be related to an inhibition of platelet adhesion. Subsequent studies have demonstrated that this is probably caused by a diminished concentration of the adhesion molecule von Willebrand factor. Nitric oxide (NO)-mediated arteriole vasodilation is also compromised in copper-deficient rats. This functional deficit to NO can be reversed by the addition of Cu, Zn-superoxide dismutase (SOD), suggesting that degradation of NO by superoxide anion occurs during copper deprivation. These observations demonstrate that dietary copper is necessary for several microvascular control mechanisms affecting inflammation, microhemostasis and regulation of peripheral blood flow.     

Diphtheria toxin fused to granulocyte-macrophage colony-stimulating factor eliminates acute myeloid leukemia cells with the potential to initiate leukemia in immunodeficient mice, but spares normal hemopoietic stem cells

We studied the cell kill induced by granulocyte-macrophage colony-stimulating factor (GM-CSF ) fused to Diphtheria Toxin (DT-GM-CSF ) in acute myeloid leukemia (AML) samples and in populations of normal primitive hemopoietic progenitor cells. AML samples from three patients were incubated in vitro with 100 ng/mL DT-GM-CSF for 48 hours, and AML cell kill was determined in a proliferation assay, a clonogenic assay colony-forming unit-AML (CFU-AML) and a quantitative long-term bone marrow (BM) culture ie, the leukemic-cobblestone area forming cell assay (L-CAFC). To measure an effect on cells with in vivo leukemia initiating potential DT-GM-CSF exposed AML cells were transplanted into immunodeficient mice. In two out of three samples it was shown that all AML subsets, including those with long-term abilities in vivo (severe combined immunodeficient mice) and in vitro (L-CAFC assay) were reduced in number by DT-GM-CSF. Cell kill induced by DT-GM-CSF could be prevented by coincubation with an excess of GM-CSF, demonstrating that sensitivity to DT-GM-CSF is specifically mediated by the GM-CSF receptor. Therefore, binding and internalization of GM-CSF probably occur in immature AML precursors of these two cases of AML. The third AML sample was not responsive to either GM-CSF or DT-GM-CSF. The number of committed progenitors of normal bone marrow (burst-forming unit-erythroid, colony-forming unit granulocyte- macrophage, and cobble stone area forming cell [CAFC] week 2) and also the number of cells with long-term repopulating ability, assayed as week 6 CAFC, were unchanged after exposure to DT-GM-CSF (100 ng/mL, 48 hours). These studies show that DT-GM-CSF may be used to eliminate myeloid leukemic cells with long-term potential in vitro and in immunodeficient mice, whereas normal hemopoietic stem cells are spared.     

Interaction of vitamins E and K: effect of high dietary vitamin E on phylloquinone activity in chicks

Age-standardised mortality rates are often used in epidemiologic studies to describe the dimension of social inequalities in mortality. This, however, conceals any age-dependence of social inequality. In an ecologic study, all causes and cause-specific mortality of all citizens of Bochum, FRG, who died 1988-1990, were evaluated using 13.171 death certificates. Data was aggregated on census tract level. The social status of a census tract was determined using 6 variables from the census 1987 describing the socio-economic situation in each census tract. Census tracts were grouped into quintiles according to their social status. Age and sex-specific mortality rates as well as rate ratios, using the quintile with the highest social status as reference, were calculated. Results for men (n = 6.288) indicate that social inequality is age-dependent for total mortality. Social differentials are especially marked for the age groups 35-64 years. For age group < 35 years and > 84 years no social differentiation in mortality is visible. Similar patterns are found with mortality from cardiovascular diseases (ICD-9: 390-459) and cancer (ICD-9: 140-208). Mortality from diseases related to health behaviour such as lung cancer or diseases associated with high alcohol intake are characterised by social inequalities above average in the middle age groups. For total mortality in women (n = 6.883) large social differentials are found for age groups 25-34 years and 45-54 years. Efforts to reduce social inequality on community level should especially be aimed at adolescents and young adults living in underprivileged areas.     

Volatile compounds produced in maiilard reactions involving glycine,ribose and phospholipid

Previous studies suggest that phospholipid affects the production of volatile heterocyclic compounds during cooking by participating in the Maiilard reaction, and also plays an important role in the formation of the characteristic aroma of cooked meat. These effects can be mimicked using aqueous model systems. The identities of 109 volatile products of model Maillard reactions involving glycine and ribose, with and without phospholipid, have been investigated using gas chromatography-mass spectrometry and the individual odours of these systems noted during sensory assessment of the effluent from the gas chromatograph. The incorporation of phospholipid increased the overall number of volatile compounds and variety of odours produced, as well as altering the nature of the dominant components and aromas.     

Schallanalyse Neuronale Repräsentation des Hörvorgangs als Basis

Zusammenfassung Anlehnend an die überlegenheit des Menschen bei der Differenzierung von Schallsignalen, verglichen mit dem aktuellen Stand der Technik, widmet sich dieser Artikel dem Aufzeigen der Mechanismen und Vorg?nge, die sich bei der Verarbeitung von mechanischem Schall in Nervenimpulse innerhalb des Ohrs vollziehen, als Basis für eine m?gliche technische Nachbildung, z.B. zur Erkennung von Tonh?hen in Musik.     

Emergent epileptiform activity in neural networks with weak excitatory synapses.

Brain electrical activity recorded during an epileptic seizure is frequently associated with rhythmic discharges in cortical networks. Current opinion in clinical neurophysiology is that strongly coupled networks and cellular bursting are prerequisites for the generation of epileptiform activity. Contrary to expectations, we found that weakly coupled cortical networks can create synchronized cellular activity and seizure-like bursting. Evaluation of a range of synaptic parameters in a detailed computational model revealed that seizure-like activity occurs when the excitatory synapses are weakened. Guided by this observation, we confirmed experimentally that, in mouse neocortical slices, a pharmacological reduction of excitatory synaptic transmission elicited sudden onset of repetitive network bursting. Our finding provides powerful evidence that onset of seizures can be associated with a reduction in synaptic transmission. These results open a new avenue to explore network synchrony and may ultimately lead to a rational approach to treatment of network pathology in epilepsy.