Ectopic Brain Tissue in Laboratory Rats

Ectopic brain tissue was detected in 11 days old rats. The anomaly was found medial and caudal of the scapula on the right chest wall appearing as a glandlike structure. Animals with ectopic brain tissue were found to have a lower relative brainweight indicating a development error in which neuroectodermal cells had been ”pinched off” and displayed early in embryonic development. Several etiological possibilities are discussed, i.e. genetic background, virusinfections, chemicals, toxinsand environmental factors. A correlation between a situation with the parameters of high temperature and low humidity versus an increased frequency of the anomaly seemed possible. As the microbiological status of the animals, food quality and most environmental factors were not known it was stated, however, that the patogenesis of the ectopic brain tissue is still unknown

Regulation of Ca2+ channel and phosphatase activities by polyamines in intestinal and vascular smooth muscle - implications for cellular growth and contractility.

Polyamines added extracellularly to intestinal and vascular smooth muscle cells cause relaxation through inhibition of Ca2+ channel activity. Intracellularly applied polyamines also affect Ca2+ channel properties. Polyamines do not readily pass over the plasma membrane because of their positive charges but in permeabilized smooth muscle preparations they have free access to the cytoplasm. In this system they increase sensitivity of the contractile machinery to Ca2+ through inhibition of myosin phosphatase activity. The magnitude of Ca2+ channel and phosphatase inhibition depends on the number of positive charges on the polyamine molecule. Polyamines have an obligatory, but yet undefined, role in regulation of cell growth and proliferation. Several groups of protein kinases, such as tyrosine and mitogen activated protein (MAP)-kinases transmit the growth signal from the plasma membrane to the cell nucleus where mitosis and protein synthesis are initiated. The data reviewed here show that polyamines may affect such signal transmission via inhibition of phosphatase activity

The G protein-coupled oestrogen receptor 1 agonist G-1 disrupts endothelial cell microtubule structure in a receptor-independent manner.

The G protein-coupled oestrogen receptor GPER1, also known as GPR30, has been implicated in oestrogen signalling, but the physiological importance of GPER1 is not fully understood. The GPER1 agonist G-1 has become an important tool to assess GPER1-mediated cellular effects. Here, we report that this substance, besides acting via GPER1, affects the microtubule network in endothelial cells. Treatment with G-1 (3 μM) for 24 h reduced DNA synthesis by about 60 % in mouse microvascular endothelial bEnd.3 cells. Treatment with 3 μM G-1 prevented outgrowth of primary endothelial cells from mouse aortic explants embedded in Matrigel. Treatment with G-1 (0.3-3 μM) for 24 h disrupted bEnd.3 cell and HUVEC microtubule structure in a concentration-dependent manner as assessed by laser-scanning confocal immunofluorescence microscopy. G-1-induced (3 μM) disruption of microtubule was observed also after acute (3 and 6 h) treatment and in the presence of the protein synthesis inhibitor cycloheximide. Disruption of microtubules by 3 μM G-1 was observed in aortic smooth muscle cells obtained from both GPER1 knockout and wild-type mice, suggesting that G-1 influences microtubules through a mechanism independent of GPER1. G-1 dose dependently (10-50 μM) stimulated microtubule assembly in vitro. On the other hand, microtubules appeared normal in the presence of 10-50 μM G-1 as determined by electron microscopy. We suggest that G-1-promoted endothelial cell anti-proliferation is due in part to alteration of microtubule organization through a mechanism independent of GPER1. This G-1-promoted mechanism may be used to block unwanted endothelial cell proliferation and angiogenesis such as that observed in, e.g. cancer

The Polyamine Pathway as a Potential Target for Vascular Diseases: Focus on Restenosis

Polyamines are organic polycations expressed by all living organisms, which are known to play an essential role in cell proliferation and differentiation. Recent studies revealed their involvement also in cell contractility and migration and in programmed cell death. These processes are known to contribute to restenosis, a pathophysiological process occurring in 10-20% of patients submitted to revascularization procedures. The advent of bare metal stents and of drug-eluting stents has significantly reduced but not eliminated the incidence of restenosis, which thus remains a clinically relevant problem. Despite the potential role of the polyamine pathway as a therapeutic target due to its involvement in proliferation, apoptosis and migration of vascular cells, experimental inhibition of polyamine synthesis and/or uptake has been poorly investigated in animal models of vascular disease. Here we review the current knowledge about molecular mechanisms related to polyamine functions, with particular reference to the role played by polyamines in vascular cell pathophysiology, together with experimental evidence obtained so far in animal models of (re) stenosis. We also evaluate the advantages of different routes of administration of polyamine synthesis/transport inhibitors and polyamine analogue molecules. Increasing knowledge about the molecular mechanisms and functions of polyamines is expected to shed new light on their potential role as a therapeutic target for restenosis reduction

The G Protein-Coupled Estrogen Receptor 1 (GPER1/GPR30) Agonist G-1 Regulates Vascular Smooth Muscle Cell Ca Handling.

The G protein-coupled estrogen receptor GPER1/GPR30 is implicated in blood pressure regulation but the mechanisms are not identified. Here, we hypothesize that GPER1 controls blood pressure by regulating vascular smooth muscle cell Ca(2+) handling. Treatment with the GPER1 agonist G-1 (in the µM concentration range) acutely reduced spontaneous and synchronous Ca(2+) spike activity in A7r5 vascular smooth muscle cells expressing mRNA for GPER1. Furthermore, G-1 (1 µM) attenuated the thromboxane A2 analogue U46619-stimulated Ca(2+) spike activity but had no effect on the U46619-induced increase in the basal level of Ca(2+). The voltage-sensitive L-type Ca(2+) channel blocker nifedipine (100 nM) reduced Ca(2+) spike activity similar to G-1. Pharmacological, but not physiological, concentrations of the estrogen 17β-estradiol reduced Ca(2+) spike activity. The GPER1 antagonist G-15 blocked G-1-induced downregulation of Ca(2+) spike activity, supporting a GPER1-dependent mechanism. G-1 (1 µM) and nifedipine (100 nM) attenuated the 30-mM KCl-evoked rise in intracellular Ca(2+) concentration, suggesting that G-1 blocks inflow of Ca(2+) via voltage-sensitive Ca(2+) channels. In conclusion, we demonstrate that the GPER1 agonist G-1 regulates vascular smooth muscle cell Ca(2+) handling by lowering Ca(2+) spike activity, suggesting a role for this mechanism in GPER1-mediated control of blood pressure. © 2013 S. Karger AG, Basel

Differences between occupations with respect to exit from working life

There is in large parts of the world a demographic crisis. Due to the increase in life length and the drop inbirth rates, prospects are that much fewer people of working age will be available in the future to supportthose in retirement.Also Sweden faces a demographic challenge, implying that it will be necessary to make the Swedeswork more years. There is an obvious potential in the age range 65-74 years, where the employment rate isa mere 15.3 percent, whereas it amounts to about 77 percent in the age range 55-64 years (StatisticsSweden 2013). The proposals under way focus on revising frameworks hampering working into old age, andcreation of economic incentives for everyone to do so. In this discussion, the role of poor working conditionsboosting premature retirement, is largely left aside. Nevertheless, it is well known that insufficient work abilityin relation to work demands is a strong predictor for early exit from working life (e.g, Ilmarinen 2011). So thequestion arises, which ones are the occupational groups that exit working life early, and are workingconditions likely to play a role

Prospective registration of symptoms and times to diagnosis in children and adolescents with central nervous system tumors: A study of the Swedish Childhood Cancer Registry

Background: The elapsed time taken to diagnose tumors of the central nervous system in children and adolescents varies widely. The aim of the present study was to investigate such diagnostic time intervals at a national level in Sweden as they correlate with clinical features. Methods: Data prospectively accumulated over a 4-year period in the Swedish Childhood Cancer Registry from patients aged 0-18 years were pooled, and diagnostic time intervals were analyzed considering tumor location, tumor type, patient age and sex, initial symptoms, and clinical timelines. All six pediatric oncology centers in Sweden contributed to collection of data. Time points for calculating the total diagnostic interval (TDI) defined as the time from symptom onset to diagnosis were reported in 257 of 319 patients (81%). Results: The time from symptom onset to the first healthcare consultation, median 2.6 weeks, did not vary significantly between patients categorized according to tumor type or location. The median TDI was 8.3 weeks for the 4-year study period. Patients with optic pathway glioma (TDI 26.6 weeks), those with tumors of the spinal cord (TDI 25.9 weeks), and those with midline tumors (TDI 24.6 weeks) had the longest lead times. Additionally, older age, too few initial symptoms, and seeking initial redress outside an emergency ward were factors associated with a longer time to diagnosis. Conclusion: This study identified several factors associated with delayed diagnosis of central nervous system tumors among Swedish children and adolescents. These novel data ought to help direct future efforts toward clinical improvement.</p

Custom, resistance and politics : local experiences of improvement in early modern England

This thesis discusses popular participation in politics in early modern England and focqses on four inter-related themes that are central to our understanding of this subject: custom, improvement, public policy and resistance. These themes have been prominent in the recent historiographies either of public policy or of social relations in early modern England, but there has, as yet, been little attempt to relate these historiographies, and still less to study their central themes in the context of local experience. Full-scale case-studies of two series of enclosure riots that occurred during the 1640s, one in Duffield Frith (Derbyshire) and the other in Whittlesey (Cambridgeshire), examine closely both the micro-politics of the defence of custom within these communities and the implications ofrecent redefinitions of 'politics'. Research was undertaken not only in national but also in local archives. Indeed the two series ofriots were specifically selected because it was evident that sufficient local records had survived to permit reconstructions of the two economies upon which 'improvement' was imposed and of social relationships within the two communities. It has, moreover, been possible to recover details of various revenueraising policies implemented by the early Stuart kings or their 'ministers that have previously been studied only briefly. The discussion synthesises the contributions ofthose historians who have done 'so much in recent years to reinvigorate the historiography ofrural social and political relations, and argues that the complex rehitionships between crown policy, local resistance and popular politics can best be reconstructed through the exploration of the micro-politics of custom. It also argues that participation in politics by ordinary people went much further than many recent historians have believed. Such participation was cohflned neither to local 'horizontal' politics, nor to 'vertical' politics in terms of petitioning parliament or waging law in the central courts, but even encompassed actively choosing to vote in parliamentary elections.EThOS - Electronic Theses Online ServiceGBUnited Kingdo