Morphological response of triclabendazole-susceptible and triclabendazole-resistant isolates of <Emphasis Type="Italic">Fasciola hepatica</Emphasis> to treatment in vitro with nitroxynil (Trodax)

Adult liver flukes belonging to three isolates of differing sensitivity to triclabendazole were incubated for 24 h in vitro in nitroxynil at a concentration of 100 μg/ml. Fine structural changes to the tegument, sub-tegumental region and gut were assessed by transmission electron microscopy. Similar changes were observed in all three isolates. In the tegumental syncytium, the basal infoldings and mitochondria were swollen, and there was an accumulation and accelerated release of secretory bodies at the apex. The crystalline core of the spines was disrupted, and the tegumental covering sloughed off. Mitochondria in the tegumental cells were also swollen, the Golgi complexes were affected and reduced numbers of T1 secretory bodies were evident in the T1-type of tegumental cell. In the sub-tegumental region, large spaces were present between cells and tissues, indicative of severe internal flooding. Swelling of mitochondria and cisternae of the granular endoplasmic reticulum was seen in the gastrodermal cells, which contained few secretory bodies. The extent of disruption varied between the isolates: the triclabendazole-resistant Sligo isolate was the most severely affected, while the Fairhurst triclabendazole-susceptible isolate was the least affected. In all three isolates, the tegument was more severely affected than the gut.     

Radial organization of developing preterm human cerebral cortex revealed by non-invasive water diffusion anisotropy MRI

Cerebral cortical development involves a complex cascade of events which are difficult to visualize in intact, living subjects. In this study, we apply diffusion tensor imaging (DTI) to the evaluation of cortical development in human infants ranging from 26 to 41 weeks gestational age (GA). Apparent diffusion of water in cortex is maximally anisotropic at 26 weeks GA and anisotropy values approach zero by 36 weeks GA. During this period, the major eigenvector of the diffusion tensor in cerebral cortex is oriented radially across the cortical plate, in accord with a predominately radial deployment of its neuronal constituents. Values for the rotationally averaged water diffusion coefficient increase between 26 and 32 weeks GA, then decrease thereafter. These changes in DTI parameters are specific to cerebral cortex and reflect changes in underlying cortical architecture and formation of neuronal connections. Because of its correlation with tissue microstructure and non-invasive nature, DTI offers unique insight into cortical development in preterm human newborns and, potentially, detection of derangements of its basic cytoarchiteture.     

Progesterone receptors A and B differentially modulate corticotropin-releasing hormone gene expression through a cAMP regulatory element

Corticotrophin-releasing hormone (CRH) plays a major role in mechanisms controlling human pregnancy and parturition. Gene regulation by progesterone may be a key point in the control of placental CRH production. Studies in primary placental ceils show that antagonism of progesterone activity or production by RU486 or trilostane leads to an increase in CRH promoter activity. This effect can be reversed by the addition of progesterone. Overexpression of progesterone receptor A (PRA) or glucocorticoid receptor resulted in a decrease in CRH promoter activity following progesterone treatment, whereas an increase in promoter activity was observed with overexpressed PR-B.     

Estrogen receptor-mediated down-regulation of corticotropin-releasing hormone gene expression is dependent on a cyclic adenosine 3＇ ,5＇-monophosphate regulatory element in human placental syncytiotrophoblast cells

Placental CRH plays a major role in the mechanisms controlling human pregnancy and parturition. Understanding how placental CRH production is regulated is therefore of importance. Previously we have shown that placental expression of CRH peptide and mRNA are inhibited by estrogens, in contrast to the stimulatory effects of estrogen on hypothalamic CRH production. Our current study found that in placental cells cotransfected with a CRH promoter construct and an estrogen receptor-alpha expression vector results in a differential regulation whereby 17beta estradiol (E2) decreased and the putative pure estrogen antagonist, ICI 182780,     

Evidence,Theory and Context: Using intervention mapping to develop a worksite physical activity intervention

Background  

The workplace is an ideal setting for health promotion. Helping employees to be more physically active can not only improve their physical and mental health, but can also have economic benefits such as reduced sickness absence. The current paper describes the development of a three month theory-based intervention that aims to increase levels of moderate intensity physical activity amongst employees in sedentary occupations.     

Steroids for intubated croup masking airway haemangioma

Recently, the beneficial role of steroids for acute laryngotracheobronchitis has been more clearly defined for both intubated and unintubated patients. However, corticosteroids also improve the clinical signs of airway haemangiomata. Two patients are described who illustrate how this can be a source of diagnostic confusion.     

Population genetics of phenylketonuria

Phenylketonuria (PKU) is an autosomal recessive disorder caused by a large number of mutations at the phenylalanine hydroxylase (PAH) locus, most of which are strongly associated with specific RFLP or VNTR haplotypes. One of the major questions remaining in PKU research is why this apparently maladaptive disorder has been maintained at a frequency of approximately 1 in 10000 among Caucasians. A growing number of studies have provided evidence that both the relatively high frequency of PKU and the strong mutation/haplotype associations might reflect the existence of multiple founding populations for PKU. Examples of putative founding populations for PKU in both Europe and Asia will be presented. Some PAH mutations are associated with multiple haplotypes, suggesting recurrence. Evidence for and against recurrence as the mechanism responsible for the association of the R408W mutation with RFLP haplotypes 1 and 2 will be discussed.