Angiogenesis: possibilities for therapeutic interventions

Vascular proliferation normally occurs only during embryonic development, the female reproductive cycle and wound healing. Various pathological conditions such as diabetic retinopathy are characterized by persistent, uncontrolled angiogenesis. At the other hand, impaired development of new blood vessels has been found to be related with myocardial infarction. A series of anti-angiogenic drugs are currently included in experimental cancer treatment, whereas the failure of ulcers to heal may be limited by increased angiogenesis upon administration of growth factors. In the present review control mechanisms of the vasculature are summarized and therapeutic approaches discussed.     

Regional anaesthesia--children are different

Is Helicobacter pylori a true carcinogen? Most carcinogens are physical, chemical or viral agents which give rise to the development of neoplasia by inducing alterations in cellular DNA. Evidence for the carcinogenic potency of such agents is usually based on dose-response curves and animal models and there is often a direct association with (epi-) genetic events. Despite the absence of such data, H. pylori has been designated as a definite cause of human cancer. This designation is largely based on epidemiological evidence. H. pylori is a carcinogen in the sense that infection with this organism induces a persistently inflamed gastric mucosa which is associated with an increased proliferative state and an increased gastric cancer risk. As such, 1-2% of the infected subjects are estimated to develop cancer, with an incidence probably close to nine times higher than that among non-infected subjects. There is a need for additional mechanistic knowledge on this association between chronic epithelial inflammation and carcinogenesis. An additional important question is whether H. pylori eradication may contribute to gastric cancer prevention. As progressive mucosal abnormalities such as atrophy and metaplasia do not regress after such intervention, the major benefit in terms of cancer prevention is likely to be to infected subjects who have not yet developed permanent gastric mucosal damage. This is in agreement with data suggesting that the role of H. pylori may be confined to the initial stages of carcinogenesis.     

Primed in situ labeling for rapid prenatal diagnosis

OBJECTIVE: Our purpose was to assess the feasibility of primed in situ labeling for analysis of prenatal diagnostic specimens. STUDY DESIGN: Prenatal diagnostic specimens were chosen at random for analysis without knowledge of clinical indication. Primed in situ labeling with primers for chromosomes 18, 21, X, and Y was performed separate from conventional cytogenetic analyses. All clinical management considerations were based solely on conventional cytogenetic analyses. RESULTS: Forty-one samples were analyzed by primed in situ labeling: 35 direct preparations of chorionic villi and 6 uncultured amniotic fluid samples. In all cases analysis confirmed the particular chromosome number determined by conventional cytogenetic analysis. CONCLUSIONS: Although conventional metaphase studies remain the standard for prenatal cytogenetic analyses, the preliminary feasibility study finds primed in situ labeling to be a rapid and reliable adjunctive diagnostic technique applicable for prenatal diagnosis in certain clinical situations. Further study is needed to assess the efficacy of primed in situ labeling in comparison to fluorescent in situ hybridization and conventional cytogenetic analyses for prenatal diagnoses.     

The role of G-CSF in mature neutrophil function is not related to GM-CSF-type cell priming

Because of uncertainties regarding the comparability of granulocyte-macrophage and granulocyte colony-stimulating factors with regard to their effects on mature neutrophils (PMNs), we compared the actions of the two cytokines on reactive oxidant production and granular secretion by these cells. We found that chemiluminescence (CL) stimulated by formylmethionyl-leucyl-phenylalanine (fMLP) was not influenced by G-CSF (0.1-100 ng/ml), whereas GM-CSF priming (10 ng/ml) caused a nearly twofold increase in this PMN response. Moreover, the reactivity of PMNs treated with GM-CSF and G-CSF in combination was not different from that of PMNs treated with GM-CSF alone. GM-CSF (10 ng/ml) increased the rate of O2- production by 79%, caused a fivefold increase in fMLP-induced myeloperoxidase (MPO) secretion, and strongly enhanced CD11b expression. In contrast, G-CSF (50 ng/ml) only slightly increased O2- production (by 15%), and MPO secretion and CD11b expression remained unchanged. Both cytokines together gave results similar to those obtained with GM-CSF alone. In the presence of platelets (which by themselves enhanced PMN reactivity), the differences in the effects of the two cytokines persisted. We conclude that the priming effect of G-CSF on mature PMNs is negligible compared with that of GM-CSF. Our results are in conflict with previous reports of much more pronounced G-CSF effects but in accord with recent work showing the failure of this cytokine to induce a range of effects produced by GM-CSF. We therefore suggest that the primary role of G-CSF in mature PMN function is still unclear but may be related to the control of PMN distribution in view of the mobilizing and marginating effects of the cytokine in vivo.     

Tetracyclines induce changes in accessibility of ribosomal proteins to proteases

It is generally assumed that folding intermediates contain partially formed native-like secondary structures. However, if we consider the fact that the conformational stability of the intermediate state is simpler than that of the native state, it would be expected that the secondary structures in a folding intermediate would not necessarily be similar to those of the native state. beta-Lactoglobulin is a predominantly beta-sheet protein, although it has a markedly high intrinsic preference for alpha-helical structure. We have studied the refolding kinetics of bovine beta-lactoglobulin using stopped-flow circular dichroism and find that a partly alpha-helical intermediate accumulates transiently before formation of the native beta-sheets. The present results suggest that the folding reaction of beta-lactoglobulin follows a non-hierarchical mechanism, in which non-native alpha-helical structures play important roles.     

Experimental analysis of the solidification of Sn–3 wt.%Pb alloy under natural convection

A quasi-two-dimensional solidification benchmark experiment with controlled thermal boundary conditions is proposed. The experiment consists in solidifying a rectangular ingot of Sn–3 wt.%Pb alloy using two lateral heat exchangers to extract the heat flux from one or two sides of the sample. The temperature difference between the two sides of the heat exchangers may vary from 0 to 40 K and the cooling rate from 0.02 to 0.04 K/s. This slow-cooling condition has been used to promote segregation formation. An array of fifty thermocouples placed on the corresponding sample walls is used to determine the instantaneous temperature distribution. During the solidification process, the temperature field is recorded versus time and analyzed. This makes it possible to estimate the change in temperature due to natural convection, the velocity field and the solidification macrostructure and segregation behavior. After each experiment, the segregation patterns are obtained by X-ray analysis and confirmed by eutectic fraction measurements. The local solute distribution is determined by means of induction coupled plasma analysis.     

Dielectric behavior of alternating ethylene,propylene, and carbon monoxide co‐ and terpolymers via impedance spectroscopy

Dielectric behavior of alternating ethylene–carbon monoxide (ECO) and ethylene–carbon monoxide/propylene–carbon monoxide elastic terpolymer (EPEC‐48) (48% mole ratio of ECO) have been investigated by impedance spectroscopy. At intermediate frequencies, the co‐ and terpolymer samples display a relaxation peak with an activation energy of 1.40 and 1.12 eV, respectively, due to a rotational motion of the carbonyl groups in the relatively more polar ECO block. However, at low frequency, a relaxation peak was observed only in the EPEC‐48 terpolymer impedance and admittance spectra due to the rotational motion of the polar groups of propylene–carbon monoxide (PCO) block which is attached to ECO repeating units. In addition, it has been found that below 100°C the ECO material is highly resistive, and both dielectric constant and loss factor are dependent on frequency and temperature. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Electrical impedance of ethylene-carbon monoxide/propylene-carbon monoxide (<Emphasis Type="Italic">EPEC</Emphasis>-<Emphasis Type="Italic">69</Emphasis>) thermoplastic polyketone

Electrical impedance technique was employed to investigate the electrical properties of ethylene-carbon monoxide/propylene-carbon monoxide terpolymer (EPEC-69). The measurements were performed in the frequency range 0.1–10⁵ Hz and in the temperature range 30–110 °C. The results reveal that the dielectric constant, loss factor, modulus, and ac conductivity are dependent of frequency and temperature. A Debye relaxation peak was detected in the plot of Z″ versus frequency where the activation energy was determined and found to be 1.26 eV. When the surface phenomenon effects were separated using the imaginary part of the complex admittance a second dielectric dispersion was observed in the low frequency region. Two models were proposed from the impedance measurements depending on temperature range.