Endothelin-Dependent Vasoconstriction in Human Uterine Artery: Application to Preeclampsia

BACKGROUND: Reduced uteroplacental perfusion, the initiating event in preeclampsia, is associated with enhanced endothelin-1 (ET-1) production which feeds the vasoconstriction of uterine artery. Whether the treatments of preeclampsia were effective on ET-1 induced contraction and could reverse placental ischemia is the question addressed in this study. We investigated the effect of antihypertensive drugs used in preeclampsia and of ET receptor antagonists on the contractile response to ET-1 on human uterine arteries. METHODOLOGY/PRINCIPAL FINDINGS: Experiments were performed, ex vivo, on human uterine artery samples obtained after hysterectomy. We studied variations in isometric tension of arterial rings in response to the vasoconstrictor ET-1 and evaluated the effects of various vasodilators and ET-receptor antagonists on this response. Among antihypertensive drugs, only dihydropyridines were effective in blocking and reversing the ET-1 contractile response. Their efficiency, independent of the concentration of ET-1, was only partial. Hydralazine, alpha-methyldopa and labetalol had no effect on ET-1 induced contraction which is mediated by both ET(A) and ET(B) receptors in uterine artery. ET receptors antagonists, BQ-123 and BQ-788, slightly reduced the amplitude of the response to ET-1. Combination of both antagonists was more efficient, but it was not possible to reverse the maximal ET-1-induced contraction with antagonists used alone or in combination. CONCLUSION: Pharmacological drugs currently used in the context of preeclampsia, do not reverse ET-1 induced contraction. Only dihydropyridines, which partially relax uterine artery previously contracted with ET-1, might offer interesting perspectives to improve placental perfusion

A Note On The Multiplicative Ratemaking Model

The multiplicative ratemaking, model we have in mind is the following one. Within a certain branch of insurance we have, say for simplicity, two tarif arguments U and V. For example, in motor insurance we could think of U and V as being make of car and geographical district respectively. In fire insurance U could be class of construction for buildings and V could relate to fire defense capacities.The arguments are of a qualitative nature and argument U has r levels, while argument V has k levels. To our disposal we have statistical experience of the business for a certain period of time, consisting of—risk exposures nij (i = 1 … r, j = 1 … k).Risk exposure nij thus corresponds to the ith U-level and the jth V-level. It could be e.g. number of policy years or sum insured during the period of observation for objects belonging simultaneously to U-level i and V-level j.The nijS are known non-random quantities.—(relative) risk measures pij(i = 1 … r, j = 1 …k).Risk measure pij could be e.g. claims frequency, i.e. number of Claims divided by number of policy years, or claims cost per policy year or claims cost as a percentage of sum insured. In general pij is thus the observed number or the observed amount of claims belonging simultaneously to U-level i and V-level j, divided by the corresponding risk exposure nij.</jats:p

On the Statistical Estimation of Costs of Claims

For a number of reasons it is important for an insurance company to estimate the claims costs of a year within the different branches of non-life insurance as soon as possible after the end of the year. The claims cost of a year is hereby defined as the total cost, before taking reinsurance into account, of all claims generated by events that have occurred during the year. When the estimation has to be done, part of these claims will be reported and closed, others will be reported and still open, and the remaining ones will be incurred but not yet reported. The total cost of the claims is defined as the sum of all payments that have been made or will be made on account of the claims. Thus, in this definition no regard is paid to interest, i.e. no discount factors are applied to payments to be made in the future.Instead of considering a year, we could consider an arbitrary period of twelve consecutive months. The estimation problem is the same, and estimates of the claims costs of consecutive twelve months periods will allow a closer following up of trends and yield predictions for the present year.For estimates to be available quickly, it is necessary that the estimation procedure be founded on data that are available immediately at the end of the year or the latest twelve months period. This means a.o. that for the bulk of the open claims, individual estimates of reserves by claims adjusters are out of the question. In other words, the estimation procedure has to be basically of a statistical character. In addition, for continuous estimates to be produced it has to be well adapted to electronic data processing. Indata to the procedure have to be stored in the memories of the computer.</jats:p

Transmission of stimulus-locked responses in two coupled phase oscillators

A model of two n:m coupled phase oscillators is studied, where both oscillators are subject to random forces, but only one oscillator is repetitively stimulated with a pulsatile stimulus. The focus of the paper is on transmission of transient responses as well as transient synchronization and desynchronization, which are stimulus locked, i.e., tightly time locked to the stimulus. A bistability or multistability of stable synchronized states of the two-phase oscillators (modulo 2pi) occurs due to the n:m coupling. Accordingly, after stimulation the two oscillators may tend to qualitatively different stable states, which leads to a cross-trial (CT) response clustering (i.e., a switching between qualitatively different poststimulus responses across trials) of either one of the oscillators or both. A stochastic CT phase resetting analysis allows one to detect such transient responses and provides a reliable estimation of the transmission time. In contrast, CT averaging (averaging over an ensemble of responses), CT standard deviation, and CT cross correlation fail in studying the transmission of such stimulus-locked responses, even in the simpler case of 1:1 coupling. In particular, even though being used as golden standard for the analysis of evoked responses in medicine and neuroscience, CT averaging typically causes severe artifacts and misinterpretations