Therapeutic patents for the treatment of pre-eclampsia

Pre-eclampsia (PE) is a pregnancy-specific syndrome that is a principal cause of maternal morbidity and mortality, accounting for almost 15% of pregnancy-associated deaths. In its mild form, PE most commonly presents with the features of maternal hypertension and proteinuria but can swiftly and unpredictably become severe with many extensive and life-threatening complications. The diverse symptoms of PE have made it a difficult disease not only to define, but also to identify a causative agent for the symptoms. It has therefore proved difficult to develop specific drugs that can be used to manage the condition. This review examines the patent literature to reveal current findings that exhibit the potential to target the effects of PE with the aim of either preventing or altering the course of this life-threatening disease of pregnancy.

Comparison of child morbidity in two contrasting medieval cemeteries from Denmark

This study compares associations between demographic profiles, long bone lengths, bone mineral content, and frequencies of stress indicators in the preadult populations of two medieval skeletal assemblages from Denmark. One is from a leprosarium, and thus probably represents a disadvantaged group (Naestved). The other comes from a normal, and in comparison rather privileged, medieval community (AEbelholt). Previous studies of the adult population indicated differences between the two skeletal collections with regard to mortality, dental size, and metabolic and specific infectious disease. The two samples were analyzed against the view known as the "osteological paradox" (Wood et al. [1992] Curr. Anthropol. 33:343-370), according to which skeletons displaying pathological modification are likely to represent the healthier individuals of a population, whereas those without lesions would have died without acquiring modifications as a result of a depressed immune response. Results reveal that older age groups among the preadults from Naestved are shorter and have less bone mineral content than their peers from AEbelholt. On average, the Naestved children have a higher prevalence of stress indicators, and in some cases display skeletal signs of leprosy. This is likely a result of the combination of compromised health and social disadvantage, thus supporting a more traditional interpretation. The study provides insights into the health of children from two different biocultural settings of medieval Danish society and illustrates the importance of comparing samples of single age groups.

Maternal label and gesture use affects acquisition of specific object names

Ten mothers were observed prospectively, interacting with their infants aged 0 ; 10 in two contexts (picture description and noun description). Maternal communicative behaviours were coded for volubility, gestural production and labelling style. Verbal labelling events were categorized into three exclusive categories: label only; label plus deictic gesture; label plus iconic gesture. We evaluated the predictive relations between maternal communicative style and children's subsequent acquisition of ten target nouns. Strong relations were observed between maternal communicative style and children's acquisition of the target nouns. Further, even controlling for maternal volubility and maternal labelling, maternal use of iconic gestures predicted the timing of acquisition of nouns in comprehension. These results support the proposition that maternal gestural input facilitates linguistic development, and suggest that such facilitation may be a function of gesture type.

A maternal influence on the conditioning to plant cues of Aphidius colemani Viereck, parasitizing the aphid Myzus persicae Sulzer

The offspring of parasitoids, Aphidius colemani Viereck, reared on Brussels sprouts and emerging from Myzus persicae Sulzer on a fully defined artificial diet, show no preferences in a four-way olfactometer, either for the odour of the diet, the odour of Brussels sprouts, or the odour of two other crucifers (cabbage and Chinese cabbage). A similar lack of odour preferences is shown when the host aphids are exposed for parasitization (for 48 h) on cabbage, Chinese cabbage or wheat. However, if parasitization occurs on Brussels sprouts, a weak but statistically highly significant response to Brussels sprout odour is observed. Although as many as 30-35% of the parasitoids show no response to any odour, another 35% respond positively to the odour of Brussels sprout compared with responses to the odours of cabbage, Chinese cabbage or wheat of only approximately 10%. An analagous result is obtained when the parent parasitoids are reared on cabbage. In this case, significant positive responses of their offspring to cabbage odour occur only if the 48-h parasitization has occurred also on cabbage. However, with parasitoids from Brussels sprouts parasitizing the aphids for 48 h also on Brussels sprouts, the offspring subsequently emerging from pupae excised from the mummies show no preference for Brussels sprout odour. Thus, although the Brussels sprout cue had been experienced early in the development of the parasitoids, they only become conditioned to it when emerging from the mummy. Both male and female parasitoids respond very similarly in all experiments. It is proposed that the chemical cue (probably glucosinolates in these experiments) is most likely in the silk surrounding the parasitoid pupa, and that the mother may leave the chemical in or around the egg at oviposition, inducing chemical defences in her offspring to the secondary plant compounds that the offspring are likely to encounter.

A longitudinal study of sero-conversion to tick-borne pathogens in smallholder dairy youngstock in Tanzania

A longitudinal study of sero-conversion of youngstock to the tick-borne pathogens Theileria parva, T mutans, Anaplasma marginale, Babesia bigemina and B. bovis was conducted over two years on smallholder dairy farms in Tanga region, Tanzania. There was evidence of maternal antibodies to all tick-borne pathogens in animals less than 18 weeks of age. Seroprevalence increased as expected with age in animals older than this but seroprevalence profiles underestimated the force of infection due to waning antibody levels between samplings. By the end of the 2-year study, less than 50% of study animals had seroconverted to each of the tick-borne pathogens investigated, consistent with the low levels of tick attachment observed on the study animals. Some associations between seroconversion to tick-borne pathogens, and counts of their known tick vectors on the animals, were identified as expected. However, some were not, suggesting that counts of some tick species may act as an index of rates of attachment of other vector species. Variation in acaricide treatment frequencies was not associated with variations in tick-borne pathogen seroprevalence suggesting that acaricides may be used more frequently than necessary on many farms. Most animals were zero-grazed, a management system associated with a significantly lower likelihood that animals seroconverted to any tick-borne pathogen exceptA. marginale. Seroprevalence varied locally with farm location (particularly for Babesia spp.) but was not well predicted by indices of ecological conditions. Our findings suggest that attempts to achieve a state of 'endemic stability' for tick-bome pathogens may be unreasonable on the smallholder dairy farms studied but reductions in the frequency of use of acaricides may be possible following prospective studies of effects on mortality and morbidity due to tick-bome pathogens. (c) 2005 Elsevier B.V. All rights reserved.

Increased apoptosis in first trimester extravillous trophoblasts from pregnancies at higher risk of developing preeclampsia

Preeclampsia complicates 5 to 10% of pregnancies and is a leading cause of maternal and fetal mortality and morbidity. Although the cause is unknown, inadequate invasion and remodeling of maternal uterine arteries by extravillous trophoblasts (EVTs) in the first trimester is a common feature. Uterine spiral artery resistance as detected by Doppler ultrasound is commonly used in the second trimester to identify pregnancies destined to develop preeclampsia. Correlation between high uterine resistance and the failure of trophoblast invasion has been reported as early as 12 weeks. However, the reason for this failure has not been established. Understanding the processes involved would significantly improve our diagnostic potential. In this study, we correlated increased first trimester uterine artery resistance with a biological abnormality in trophoblast function. EVTs derived from high-resistance pregnancies were more sensitive to apoptotic stimuli than those from normal-resistance pregnancies. Survival of EVTs from high-resistance pregnancies could be increased by nitric oxide, whereas inhibition of nitric oxide in cells from normal-resistance pregnancies increased apoptotic sensitivity. This predates the onset of symptoms by several weeks and provides evidence for a mechanism responsible for the incomplete uterine vessel remodeling and the differences in artery resistance between preeclamptic and normal pregnancies.

The measurement of maternal plasma corticotropin-releasing factor (CRF) and CRF-binding protein improves the early prediction of preeclampsia

In the present study we measured maternal plasma concentrations of two placental neurohormones, corticotropin-releasing factor (CRF) and CRF-binding protein (CRF-BP), in 58 at-risk pregnant women consecutively enrolled between 28 and 29 wk of pregnancy to evaluate whether their evaluation may predict third trimester-onset preeclampsia ( PE). The statistical significance was assessed by t test. The cut-off points for defining altered CRF and CRF-BP levels for prediction of PE were chosen by receiving operator characteristics curve analysis, and the probability of developing PE was calculated for several combinations of hormone testing results. CRF and CRF-BP levels were significantly ( both P < 0.0001) higher and lower, respectively, in the patients (n = 20) who later developed PE than in those who did not present PE at follow-up. CRF at the cut-off 425.95 pmol/liter achieved a sensitivity of 94.8% and a specificity of 96.9%, whereas CRF-BP at the cut-off 125.8 nmol/liter combined a sensitivity of 92.5% and a specificity of 82.5% as single markers for prediction of PE. The probability of PE was 34.5% in the whole study population, 93.75% when both CRF and CRF-BP levels were changed, and 0% if both hormone markers were unaltered. The measurement of CRF and CRF-BP levels may add significant prognostic information for predicting PE in at-risk pregnant women.

Preventing drug related morbidity: a process for facilitating changes in practice

Aim: To describe how quantitative data obtained from applying a series of indicators for preventable drug related morbidity (PDRM) in the electronic patient record in English general practice can be used to facilitate changes aimed at helping to improve medicines management. Design: A multidisciplinary discussion forum held at each practice facilitated by a clinical researcher. Subjects and setting: Eight English general practices. Outcome measures: Issues discussed at the multidisciplinary discussion forum and ideas generated by practices for tackling these issues. Progress made by practices after 1, 3, and 6 months. Results: A number of clinical issues were raised by the practices and ideas for moving them forward were discussed. The issues that were easiest and most straightforward to deal with (for example, reviewing specific patient groups) were quickly addressed in most instances. Practices were less likely to have taken steps towards addressing issues at a systems level. Conclusions: Data generated from applying PDRM indicators can be used to facilitate practice-wide discussion on medicines management. Different practices place different priority levels on the issues they wish to pursue. Individual practice "ownership'' of these, together with having a central committed figure at the practice, is key to the success of the process.