Pyrazolinone analgesics prevent the antiplatelet effect of aspirin and preserve human platelet thromboxane synthesis.

BACKGROUND: Anti-inflammatory analgesics, including ibuprofen and naproxen, are known to interfere with the antiplatelet effect of aspirin, presumably as a result of a drug-drug interaction at the level of platelet cyclooxygenase-1 (COX-1). OBJECTIVE: We studied whether dipyrone, which has recently been reported to inhibit COX isoforms by a mechanism different from conventional non-steroidal anti-inflammatory drugs (NSAIDs), also interferes with the antiplatelet effect of aspirin. METHODS: Arachidonic acid- and collagen-induced aggregation, as well as thromboxane formation, were measured in human platelet-rich plasma. Platelet P-selectin expression was determined by flow cytometry and cell-free COX enzyme activity was quantified by luminol-enhanced luminescence of human platelet microsomes. In addition, computerized docking was performed based on the crystal structure of COX-1. RESULTS: 4-Methylaminoantipyrine (MAA), the active metabolite of dipyrone, largely attenuated or even completely abolished the inhibition of arachidonic acid-induced platelet aggregation, thromboxane formation and P-selectin expression by aspirin. Similar results were obtained for other pyrazolinones, as well as for the conventional NSAIDs ibuprofen and naproxen. Moreover, MAA attenuated the effect of aspirin on COX activity of platelet microsomes, suggesting a competition with aspirin at the COX-1 enzyme. This was confirmed by docking studies, which revealed that MAA forms a strong hydrogen bond with serine 530 within the COX-1, thereby preventing enzyme acetylation by aspirin. CONCLUSION: This study demonstrates for the first time that dipyrone and other pyrazolinones have a high potential to attenuate or prevent the antiplatelet effect of aspirin. This should be considered if pyrazolinone analgesics are administered to patients with cardiovascular disease requiring antiplatelet aspirin therapy.

Suicide after deployment in UN peacekeeping missions--a Danish pilot study.

This pilot study looks at the frequency of suicide among Danish soldiers who took part in the UN mandated forces (UNMF) during the 1990's. In a contingent of nearly 4000 Danish UN soldiers four suicides were documented, two of whom committed suicide less than one month before deployment and two who committed suicide within a year after discharge from mission. Contributing factors, prevention strategies, and implications for future research are discussed.

Postponed suicide death? Suicides around birthdays and major public holidays.

The relationship between suicide and birthdays, and suicide and public holidays has been studied from data on 32,291 Danish suicides by persons ages 15 years and older in the 25-year period 1970-1994. Evidence was found to support the theory of the "broken-promise effect" for major public holidays in that there appears to be a postponement of a significant number of suicides from before a holiday until after. The division of holidays into nonworking and (half-time) working days showed that a "holiday effect" could only be found around major public holidays, particularly Christmas, Easter, and Whitsun. The postponing or transpositioning effect is relevant to prevention, especially because of the availability and accessibility of help at the end of and after major public (nonworking) holidays.

Attempted suicide and major public holidays in Europe: findings from the WHO/EURO Multicentre Study on Parasuicide.

OBJECTIVE: The aim of the study was to examine the relationship between suicide attempts and major public holidays in Europe. METHOD: The analysis was based on data on 24 388 suicide attempts by persons aged 15 years or older in the period 1989-1996. Data from 13 centres (representing 11 countries) participating in the WHO/EURO Multicentre Study on Parasuicide were analysed. The analysis of the fluctuation of suicide attempts around public holidays was based on the daily number of suicide attempts for each centre. For each day in the period under examination a mean number of suicide attempts (mu) was calculated. The analysis was based on the assumption that the data followed a Poisson distribution. The observed number of daily suicide attempts was compared with the expected number of attempts. A multiplicative model for the expected number in each centre was developed. RESULTS: Before Christmas there were fewer suicide attempts than expected, and after Christmas there were approximately 40% more attempts than expected. In addition, more attempts than expected were registered on New Year's Day. In countries where people have the day off work on Whit Monday there were significantly fewer attempts during the 3 days before, but where Whit Monday is a normal working day significantly fewer attempts occurred on the Monday to Wednesday after Whit Sunday. CONCLUSION: There appears to be a transposition of a significant number of suicide attempts from before (and during) a major public holiday until after it. The division of holidays into non-working and working days showed that a 'holiday effect' could only be found around major public holidays, particularly Christmas, Easter and Whitsun. These findings support the theory of the 'broken-promise effect' for major public holidays.

The development of nonpeptide angiotensin II receptor antagonists: a success story.

The modulation of the renin-angiotensin system continues to be an important target in drug design. The development of nonpeptide angiotensin II receptor antagonists offers a new tool in treatment of hypertension. Starting from benzimidazole lead structures detailed structure-activity analyses, molecular modeling methods, and dedicated syntheses led to the development of potent, orally active antihypertensive drugs.

[Suicidal thoughts and suicidal attempts among 15-24 years old individuals in the Danish educational system]. / Selvmordstanker og selvmordsforsøg blandt 15-24-årige i det danske uddannelsessystem.

The purpose of the study is by the instrumentality of an anonymous and voluntary interview study to expose the extent of suicidal ideation and suicide attempts among 15-24-year-olds in the Danish educational system. 3042 persons participated in the study. About 40% of those interviewed had at least once had suicidal ideation and almost one in every twenty confirmed that they had attempted to commit suicide. Furthermore, the study showed that almost one in every ten had experienced suicide in the family. The study showed that frequent or chronical suicidal ideation and self-destructive behaviour can be considered risk factors of suicide attempts and possible predictors of future suicidal behaviour. It also appeared that the students who had experienced suicide in the family had a risk of committing suicide that was three times as high as that of the students who had not experienced suicide in the family. The results of the study also suggest that it is probably only the tip of the iceberg which is detected or registered by the treatment system. To all appearance, close on 75-90% of young suicide attempts are not registered officially. This bears witness of the fact that many of these 15-24-year-olds apparently received no help after their suicide attempt.

Parasuicide in the Nordic countries.

This article gives an account of some findings of the WHO/EURO multicentre study on parasuicide from the five Nordic centres: Helsinki (Finland), Stockholm (Sweden), and the countries of Funen (Denmark), Sø-Trøndelag (Norway) and Västerbotten (Sweden). For parasuicide patients treated in hospital in these five Nordic centres, the parasuicide rates per 100,000 inhabitants per annum were 222 for women, 213 for men and 224 for both sexes combined. In all the Nordic centres except Helsinki, women had higher parasuicide rates than men. The female/male parasuicide ratio was 1.16 for all Nordic centres. The highest parasuicide rates in the whole material were found in Helsinki, Stockholm and Funen, and the lowest in Sør-Trøndelag and Västerbotten. The highest parasuicide rates lay in the 30-39 age interval, i.e. the peak of parasuicide rates was in older age groups than previously reported. Single people, especially divorcees and those who have never been married, constitute a high-risk group in both sexes. The risk of parasuicide for single men is three times that for married men in all the Nordic centres except Sør-Trøndelag, where the risk is five times higher. The parasuicide risk for single women is twice as high as for married women except for women in Funen, where the risk for single and married women is almost equal. Exceptionally high parasuicide rates are also reported for Finnish citizens in Sweden, compared with Finns from the Helsinki centre. Parasuicide rates appear to be correlated with population density, since the densely populated areas of Helsinki, Stockholm and Funen evince higher parasuicide rates than the sparsely populated areas of Sør-Trøndelag and Västerbotten.

Suicide in Denmark, 1922-1991: the choice of method.

The authors describe methods of suicide registered in Denmark during the last 70 years. The preferred method was initially hanging then later poisoning, first mainly with household gas, later with other agents, especially overdoses of medicine. In recent years there has, however, also been an increasing number of hangings, drownings and other methods of suicide, and there seems to be an increasing inclination towards selecting more violent methods. The Danes' choice of method for committing suicide differ somewhat from that in the other Scandinavian countries; in particular, there have been far more cases of self-poisoning in Denmark.

[Suicide in Denmark over 70 years, 1922-1991. General tendencies]. / Selvmord i Danmark gennem 70 år, 1922-1991. Generelle tendenser.

The frequency of suicide in Denmark has been studied for a period of 70 years. Rates of suicide per 100,000 inhabitants, 15 years and over, by age and sex have been calculated, the calculation being based on data from the Danish Cause-of-Death statistics and from the Population statistics provided by Danmarks Statistik. Although the frequency of suicide has varied during the period under study, the overall trend has been one of significant increase. The increase is in great part due to the fact that an increasing number of women, especially women in their 50s, commit suicide. The increase in male rates is more evenly distributed over all age groups and, contrary to what is the case for women, the age-effect is still strong for men.

Suicide among the Danish elderly: now and in years to come.

The growing number of elderly people is causing concern in most western countries, and the fear is being expressed that the changing age distribution of the population might eventually lead to increasing frequencies of suicide among old people. The authors discuss the developments in the age distribution of the Danish population and forecasts for the frequency of suicide among the elderly. The presumption that rates of suicide among the elderly will go up is questioned by pointing to the fact that the alleged dysfunctions caused by the growth in the population of elderly people may at least to some extent be counterbalanced by the fact that a new "type" of elderly person appears to be entering the stage.

Repeated suicidal behavior: a two-year follow-up.

The majority of suicide attempters repeat the suicidal act at least once. The study described here on a Danish sample of suicide attempters shows that 31% had made only one attempt. More repeaters than nonrepeaters were divorced, and more repeaters also lived alone or alone with children. The two groups did not differ significantly as to level of education, but were clearly different with regard to their economic activity. These differences cannot be used as a basis for the prediction of future suicidal behavior, since the factors discussed refer to characteristics that define suicide attempters in general. However, they do point to conditions that might be targets for intervention and aftercare.

The frequency of suicide in individual Danish birth cohorts, 1922-1991.

In recent years many suicidologists have based their epidemiological studies on suicide on theories assuming that people born within the same period of time will follow the same suicidal patterns throughout their lives, and that variations in the annual rate of suicide will, therefore, reflect systematic differences between cohorts. Cohort analysis carried out on Danish data showed, however, that although some differences could be found as to the course of events during the life span of the cohorts and also when the material was adjusted for sex, no significant differences could be found between various birth cohorts in the total rates of suicide. The authors argue that the reason for this is that a cohort effect is only one of three dimensions of an analytical tool, namely, Age-Period-Cohort (APC) analysis, and that the balance between the three effects changes over time.

Corticotropin-releasing factor (CRF): mechanism to elevate mean arterial pressure and heart rate.

The efferent mechanisms by which central administration of corticotropin-releasing factor (CRF) elevates mean arterial pressure and heart rate were assessed in unanesthetized, unrestrained rats. CRF increased blood pressure and heart rate by stimulating noradrenergic sympathetic nervous outflow. CRF-induced cardiovascular changes were not dependent on anterior pituitary hormone release, adrenomedullary epinephrine secretion, the renin-angiotensin system or circulating vasopressin.

Intussusception of the mid-jejunum after small intestinal bypass operation for obesity: case report.

Invagination of the defunctionalized small intestine after jejunoileal bypass operation for morbid obesity is a serious but rare complication since the introduction of Wills' technique. The possibility, however, still exists of mechanical obstruction of other parts of the defunctionalized small intestine. This occurred in a 25-yr-old man on several occasions during an interval of 1 to 3 yr after the primary operation.