The return of the pharmaceutical industry to the market of contraception

In the 1980s and 1990s, the litigious climate in the US had a catastrophic effect on sales of many major contraceptives. Although oral contraceptives escaped controversy, the intrauterine device (IUD) and Norplant(R) were two targets of damaging litigation. The IUD was withdrawn from the market in 1985. Since 1994 when the attacks began against Norplant, its US sales have dramatically declined, even though no fault has been found in the method or its development. In general, pharmaceutical companies were extremely hesitant to develop new contraceptives during this period. The bleak outlook, however, began to shift in the late 1990s, as fertility rates began to decrease worldwide and contraceptive users increased. By 2025, 2500 million women will comprise the customer base for contraception. Global pharmaceutical companies are now participating in expanding markets overseas and have launched and continue to develop a range of new long-term reversible, and highly effective, contraceptive products outside the traditional oral contraceptive field. Two new contraceptives on the way to the US market are: Mirena, a levonorgestrel-releasing intrauterine system manufactured by Schering-Leiras; and Implanon, a single implant system manufactured by Organon of the Netherlands. Other birth control methods soon to be launched include: emergency contraceptives, the contraceptive patch, monthly contraceptive injections, mifepristone for medical abortion, and modified oral contraceptives.     

Recurrence of Venous Thromtoembolic Disease and Use of Oral Contraceptives

In 1969 this department reported on 42 women who had developed “idiopathic” venous thromboembolism while using oral contraceptives and 42 women who had developed the disease in the absence of such exposure. We have traced the subsequent history of these women to obtain information about recurrence of the disease.During the follow-up period the risk of recurrence of thromboembolism during pregnancy or the puerperium appeared to be much the same irrespective of whether or not oral contraceptives had been in use at the time of the index attack. Recurrences unassociated with childbearing however, occurred about four times more often among women who had not been using oral contraceptives at the time of the index attack than among women who had been doing so. None of these findings was influenced by the use of oral contraceptives during the follow-up period, since exposure to the preparations was negligible after the index attack.     

Determinants of current contraceptive use and method choice in Mongolia

This study examines the determinants of current contraceptive use and method choice in Mongolia using data from the 1998 Mongolian Reproductive Health Survey and 2000 Mongolian Population and Housing Census. Since 1976, access to modern contraceptives has been liberalized and all restrictions on the use, distribution and import of contraceptives were removed in 1989. There were some increases in the use of modern contraceptives among married women in the 1990s; however, at the start of the twenty-first century the IUD and periodic abstinence remain the most widely used methods. Women with higher levels of education are more likely to be current users of contraception, and if they are current users, they are more likely to choose the IUD and traditional methods. Women living in rural areas have a higher probability of using contraception and are more likely to choose the IUD and traditional methods. Significant variations exist between primary sampling units in current contraceptive use and in the choice of modern methods. Community-level variables were important predictors in reducing variation between primary sampling unit, when other modern methods were compared with traditional methods.     

Proceedings: Correlation of various clinical parameters with glucose tolerance test in women using oral contraceptives

A study was carried out to determine whether oral contraceptives affect carbohydrate metabolism as assessed by glucose tolerance curves. Glucose tolerance tests were carried out in seventy-six women. The women were divided into two groups. The first group constituted the control and the second group comprised women taking combination oral contraceptives. The glucose tolerance curves were correlated with: (1) the duration of thereapy; (2) the family history of diabetes; (3) the obstetric history; (4) age: (5) weight gain; (6) parity; and (7) changes in blood pressure. The combination type of oral contraceptives were observed to affect adversely the glucose tolerance test. A significant correlation was recorded between the familial diabetic history, intake of combination contraceptives and abnormal glucose tolerance tests. A history of birth of a large baby was found to be an important indicator of abnormal values of glucose tolerance in women taking a combination type of oral contraceptive. Such women showed an abnormal curve pattern at a much earlier age in life compared with controls. It was also observed that a high percentage of women who had gained excessive weight on combination contraceptives had an altered glucose tolerance test. Parity and blood pressure were two parameters which did not reveal any correlation with abnormal glucose tolerance curves.     

Nongenital malformations following exposure to progestational drugs: the last chapter of an erroneous allegation

In the late 1960s and 1970s, a number of epidemiological studies were published indicating that pregnant women who were exposed to an array of sex steroids delivered infants with an increased incidence of nongenital congenital malformations. Because of these publications, the Food and Drug Administration (FDA), in conjunction with various pharmaceutical companies, labeled the therapeutic exposure of progestational drugs and contraceptives in pregnant women as a risk factor for limb‐reduction defects (LRDs) and congenital heart defects (CHDs). Subsequently there was a rapid decrease in the exposure of pregnant women to these drugs and the initiation of numerous lawsuits alleging that a particular progestational drug was responsible for a child's nongenital congenital malformation. Wilson and Brent ( 1981 ) published an article indicating that epidemiological and animal studies of these drugs, and basic science did not support the package insert's warnings. Many new and previous animal and epidemiological studies did not support the FDA box warning. In 1987 the FDA held a hearing in which the FDA, the Teratology Society, the Centers for Disease Control and Prevention, the American College of Obstetrics and Gynecology, and other organizations supported the position that progestational agents did not result in nongenital malformations. An editorial appeared in Teratology congratulating the FDA for removing the warning label on oral contraceptives regarding nongenital malformations. In 1999 the FDA published new wording for package inserts that removed warnings for nongenital malformations for all progestational agents. In spite of the recent changes in the package inserts, lawsuits have alleged that progestational drugs cause nongenital malformations. It took 22 years from the time a box warning was required by the FDA until the warnings were removed in 1999. The 1999 FDA publication, which is a scholarly and objective document, should put an end to 2 decades of concern and anxiety for pregnant women or women of reproductive age. Could scientists, the pharmaceutical companies, or the FDA have prevented the mislabeling of progestational drugs with regard to their teratogenic risks? Was the epidemiological or teratology community at fault because they did not critique and respond to the early publications? Did the FDA act too slowly? The epidemiologic analyses, animal studies, and basic science principles have been reviewed, and it is obvious that clinically utilized progestational drugs do not cause nongenital malformations (i.e., LRDs and CHDs). Birth Defects Research (Part A) 2005. © 2005 Wiley‐Liss, Inc.     

The Changing Landscape for Paediatric Regulation of Pharmaceutical Agents with a Focus on Antifungal Agents

The limited paediatric specific data for pharmaceutical agents has been a persistent issue for over a century. Since the late 1990s, two of the world’s largest regulatory agencies, the Food and Drug Administration and the European Medicines Agency, have made concerted efforts backed by federal legislation aimed to improve the availability of paediatric data for many pharmaceutical agents. In the same time frame, there has been considerable research and development of new antifungal agents to help combat life-threatening invasive fungal disease. The evolving landscape of pharmaceutical regulation has helped to establish paediatric appropriate dosing recommendations for a number of these antifungal agents. However, the process by which paediatric data are realized is still too slow often leaving years between the initial adult approved indication and subsequent paediatric indications. This delay in paediatric data continues to perpetuate off-label use of many antifungal therapies in children, which can have negative consequences. As we strive to improve the availability of paediatric data for pharmaceutical agents, there needs to be a focus on timely delivery of these data to eliminate the window between adult and paediatric indications.     

Experimental history and Herman Boerhaave’s chemistry of plants

In the early eighteenth century, chemistry became the main academic locus where, in Francis Bacon’s words, Experimenta lucifera were performed alongside Experimenta fructifera and where natural philosophy was coupled with natural history and ‘experimental history’ in the Baconian and Boyleian sense of an inventory and exploration of the extant operations of the arts and crafts. The Dutch social and political system and the institutional setting of the university of Leiden endorsed this empiricist, utilitarian orientation toward the sciences, which was forcefully propagated by one of the university’s most famous representatives in the first half of the eighteenth century, the professor of medicine, botany and chemistry Herman Boerhaave. Recent historical investigations on Boerhaave’s chemistry have provided important insights into Boerhaave’s religious background, his theoretical and philosophical goals, and his pedagogical agenda. But comparatively little attention has been paid to the chemical experiments presented in Boerhaave’s famous chemical textbook, the Elementa chemiae, and to the question of how these experiments relate not only to experimental philosophy but also to experimental history and natural history, and to contemporary utilitarianism. I argue in this essay that Boerhaave shared a strong commitment to Baconian utilitarianism and empiricism with many other European chemists around the middle of the eighteenth century, in particular to what Bacon designated ‘experimental history’ and I will provide evidence for this claim through a careful analysis of Boerhaave’s plant-chemical experiments presented in the Elementa chemiae.     

Turmeric: old spice,new spice

The history of chemical investigations into the yellow components of turmeric can be traced from 1815. Although the major yellow component of turmeric, curcumin, often is represented as a 1,3-diketone in the solid state and in nonaqueous solution, it exists in the enol form. The struggle to identify the chemical structure of curcumin continued for nearly a century and was complicated by the difficult purification of curcumin and by the presence of two additional yellow components. Food remains the main use for turmeric (old spice); its use as a dye has diminished since the 19th century, but it may have pharmaceutical uses (new spice).     

Seabed dynamics in a lage coastal embayment: 180 years of morphological change in the outer Thames estuary

This article analyses the morphological history of the outer Thames seabed, covering over 3,000 km² from Aldeburgh (Suffolk), to Southend-on-Sea (Essex) and Margate (Kent). The region has been depicted on bathymetric charts since the sixteenth century, and has been formally charted since the eighteenth century. Charts published since the early 1800s incorporate sufficient grid reference or ground control detail for georectification onto a common coordinate system (British National Grid). The morphological history of the outer seabed was thus reconstructed through the digitisation and interpolation of soundings onto a regular grid (3D surface). The evolution of seabed morphology was examined using transects, bathymetric change maps and spatial statistics. The results show considerable spatial variability in seabed behaviour. Within the central Thames, banks have experienced significant depth changes can be associated with lateral shifts in individual banks. Some of the outer banks in this region exhibit progressive elongation. Shifts in bank position across the Suffolk shoreface appear to be more subtle, and there is evidence here of both onshore and offshore migration. There is no clear evidence of any regionally coherent response to large-scale historical forcing such as sea-level rise.     

Action mechanism of insulin-mimetic vanadyl-allixin complex

In the 21st century, there has been a dramatic worldwide increase in the prevalence of metabolic syndromes, including diabetes mellitus (DM). Several synthetic pharmaceutical agents have been developed and used for the treatment of type-2 DM; however, these compounds have several problems such as side effects, hypoglycemia, and weight gain. Therefore, new drugs are required for DM therapy. We have proposed that some vanadyl complexes function as potent insulin-mimetic and antidiabetic agents in type-1 and type-2 DM animal models. In this article, we review the possible action mechanism of insulin-mimetic and antidiabetic vanadyl complexes, focusing on a recently proposed complex, bis(allixinato)oxovanadium(IV), with respect to the insulin-signaling pathway in cultured adipocytes.     

An objective view of biological diversity: how history and epistemology shaped current treatment

The concept of biological diversity has inspired important discussions throughout the history of ecology. Although its meaning and usefulness have been questioned, it is currently one of the key artifacts of ecology. One way to try to understand why such a concept has undergone so many discussions is to examine its emergence and history from the epistemology perspective. In the present work, we investigated how the emergence of mechanical objectivity (as an epistemic virtue) and trained judgment affected how ecologists address the concept of biological diversity. Thus, we employed the theoretical framework of objectivity (provided by Daston and Galison in Objectivity. Zone Books, New York, 2007) to analyze different periods of scientific literature in ecology (“initial period”: end of the nineteenth century and beginning of the twentieth century; “intermediate period”: mid-twentieth century; “contemporary period”: from the second half of the 1980s). Our results showed that the emergence of mechanical objectivity and trained judgment affected biological diversity research. In particular, the ideal of objectivity behind the way in which the concept of biological diversity is addressed in different fields of contemporary ecology could not be the same.     

Visual arts education provisions for primary schools in Turkey

This article examines the history of art education in Turkey. Since the beginning, the purposes of the arts and art education have been a point of discussion by various authorities. Whether art education should be taught, and how it needs to be taught, have been at the forefront of educationalists' minds. As a result, introducing certain models of art education has been a challenge. The objective of this article is to present the changes in art education since the 19th century in Turkey. The main focus is on art education practices and policies and an overview of key events in Turkey's history of art education. The article also presents issues related to the importance of visual arts education in Turkish primary school settings. In so doing, this research aims to show readers how past developments helped to create the current visual art education policy in Turkey.     

Oral contraceptives and fatal subarachnoid haemorrhage.

A case-control study was conducted of the deaths from subarachnoid haemorrhage (SAH) in women aged 15-44 in England and Wales in 1976. There was a small excess of oral contraceptive use by the women who died from SAH compared with their generally healthy practice-matched controls; this was not, however, statistically significant. Out of 134 women who died from SAH, 34 had a history of hypertension compared with only six of their controls. Renal disease and pre-eclamptic toxaemia were more commonly associated with hypertension in the dead women than in controls. No change in the annual mortality from SAH has been observed in the past 20 years such as might have been expected if the risks were high. Although current or past use of oral contraceptives may have increased the blood pressure and risk of SAH in a few women, the most important factor in determining this risk was hypertension. SAH should thus probably not be regarded as serious cause for concern in healthy non-hypertensive women using oral contraceptives.     

Blood pressure and contraceptive use

In a survey of 461 women routinely attending family planning clinics those taking oral contraceptives had significantly higher mean systolic and diastolic blood pressures than those using non-hormonal contraception. There appeared to be a dose-response relation of blood pressure to the progestogen component of two oral contraceptives with an identical 30 μg ethinyloestradiol component. This supports the idea that the progestogen as well as the oestrogen component has an aetiological role in the rise in blood pressure. There was a significant correlation of blood pressure with duration of current use of oral contraceptive but not with total duration of use. There was also a significant negative correlation of blood pressure with time since oral contraceptives were last taken, and women who had stopped using oral contraceptives over a month previously had similar blood pressures to those who had never taken them. In women taking oral contraceptives those who had either a history of hypertension in pregnancy or a family history of hypertension had significantly higher mean blood pressures than those who did not. Both systolic and diastolic blood pressures correlated independently with weight and body mass index, but controlling for the effect of this and age did not affect the above relations. No significant differences in mean blood pressures were found between different ethnic groups, and there was no relation of blood pressure to reported marital state, social class, parity, smoking, or alcohol use.Any oral contraceptive that has a less adverse effect on blood pressure has implications for general prescribing policy; thus even small differences in the progestogen contents of low-dose oestrogen pills may be important.     

Phenolic glycosides of the Salicaceae and their role as anti-herbivore defenses

Since the 19th century the phytochemistry of the Salicaceae has been systematically investigated, initially for pharmaceutical and later for ecological reasons. The result of these efforts is a rich knowledge about the phenolic components, especially a series of glycosylated and esterified derivatives of salicyl alcohol known as “phenolic glycosides”. These substances have received extensive attention with regard to their part in plant-herbivore interactions. The negative impact of phenolic glycosides on the performance of many generalist herbivores has been reported in numerous studies. Other more specialized feeders are less susceptible and have even been reported to sequester phenolic glycosides for their own defense. In this review, we attempt to summarize our current knowledge about the role of phenolic glycosides in mediating plant-herbivore interactions. As background, we first review what is known about their basic chemistry and occurrence in plants.     

Plant identification credibility in ethnobotany: a closer look at Polish ethnographic studies

In Italy, malaria was an endemic disease that was eradicated by the mid-20th century. This paper evaluates the prophylactic and therapeutic remedies used by folk medicine to cure malaria in Calabria (southern Italy). The data has been collected by analysing works of physicians, ethnographers, folklorists and specialists of the study of Calabrian history between the end of the 19th century and the 20th century. The data collected have allowed us to describe the most common cures used by the Calabrian people to treat malaria and the most evident symptoms of this disease, such as intermittent fever, hepato-spleenomegaly, asthenia and dropsy. This approach uncovered a heterogeneous corpus of empirical, magical and religious remedies, which the authors have investigated as evidences of past "expert medicine" and to verify their real effectiveness in the treatment of malaria.     

Solid phase synthesis of complex natural products and libraries thereof.

Natural products have served as an important source of medicinal compounds and pharmaceutical leads over the last century. Within the last 10 years, significant interest has developed in applying combinatorial chemistry techniques to the study of natural products and their biological activities. In this review, we examine several representative efforts wherein natural product skeletons have been constructed or immobilized on solid support and subsequently derivatized, giving rise to analog libraries useful in understanding the structure-activity relationships of the parent natural product. Issues such as target selection, library design, linker development, automation, and library characterization are addressed.     

Nematode-Applied Technology for Human Tumor Microenvironment Research and Development

Nematodes, such as Caenorhabditis elegans, have been instrumental to the study of cancer. Recently, their significance as powerful cancer biodiagnostic tools has emerged, but also for mechanism analysis and drug discovery. It is expected that nematode-applied technology will facilitate research and development on the human tumor microenvironment. In the history of cancer research, which has been spurred by numerous discoveries since the last century, nematodes have been important model organisms for the discovery of cancer microenvironment. First, microRNAs (miRNAs), which are noncoding small RNAs that exert various functions to control cell differentiation, were first discovered in C. elegans and have been actively incorporated into cancer research, especially in the study of cancer genome defects. Second, the excellent sense of smell of nematodes has been applied to the diagnosis of diseases, especially refractory tumors, such as human pancreatic cancer, by sensing complex volatile compounds derived from heterogeneous cancer microenvironment, which are difficult to analyze using ordinary analytical methods. Third, a nematode model system can help evaluate invadosomes, the phenomenon of cell invasion by direct observation, which has provided a new direction for cancer research by contributing to the elucidation of complex cell–cell communications. In this cutting-edge review, we highlight milestones in cancer research history and, from a unique viewpoint, focus on recent information on the contributions of nematodes in cancer research towards precision medicine in humans.     

Ergot: from witchcraft to biotechnology

The ergot diseases of grasses, caused by members of the genus Claviceps , have had a severe impact on human history and agriculture, causing devastating epidemics. However, ergot alkaloids, the toxic components of Claviceps sclerotia, have been used intensively (and misused) as pharmaceutical drugs, and efficient biotechnological processes have been developed for their in vitro production. Molecular genetics has provided detailed insight into the genetic basis of ergot alkaloid biosynthesis and opened up perspectives for the design of new alkaloids and the improvement of production strains; it has also revealed the refined infection strategy of this biotrophic pathogen, opening up the way for better control. Nevertheless, Claviceps remains an important pathogen worldwide, and a source for potential new drugs for central nervous system diseases.