Placental anatomy and diffusing capacity in guinea pigs following long-term maternal hypoxia

To determine the relation of placental structure to placental diffusing capacity (DPCO), we exposed Hartley guinea pigs to 12 or 14 per cent O2 from day 15 of gestation to near term (64 days). At that time we measured DPCO and fetal body and placental weights. In addition, we used stereological techniques to measure placental parameters important to diffusing capacity. We also used a mathematical model with results from the stereological measurements to predict the diffusing capacity. In the first hypoxic group (E1), measured DPCO decreased 10.1 +/- 3.7 per cent, while that predicted was 2.4 per cent less than control. Total vascular volume decreased 6.6 +/- 3.6 per cent, while tissue volume and mean diffusion distance increased 10.2 +/- 5.6 per cent and 12.9 +/- 7.0 per cent, respectively. In the pair-fed animals, measured DPCO decreased 22.6 +/- 4.6 per cent, while that predicted was 20.0 per cent less than control. There were no significant stereological differences in this group. In the second (E2) hypoxic group, measured DPCO increased 27.2 +/- 7.4 per cent, while that predicted increased 38.2 per cent. For this same group, total vascular volume increased 11.7 +/- 3.0 per cent, and tissue volume and mean diffusion distance decreased 18.2 +/- 4.6 per cent and 17.8 +/- 3.8 per cent, respectively. These results demonstrate the dependence of placental diffusing capacity upon placental structure.     

Using an interactive chemotherapy training package to improve patient safety

All health-care professionals involved in the use of cytotoxic chemotherapy, if they are to avoid serious harm to patients, can benefit from an interactive training package in the safe use of these drugs. This article discusses a pilot study of a training CD-ROM which was undertaken in a cancer unit.     

Areal and synaptic interconnectivity of prelimbic (area 32), infralimbic (area 25) and insular cortices in the rat

This study investigated the interconnectivity of areas in the medial prefrontal and insular cortices in the rat. The areas studied were the prelimbic (PL, area 32) and infralimbic (IL, area 25) cortices and the dorsal anterior agranular insular (AId) and regions of posterior insular cortex (PI-comprising the agranular, dysgranular and granular fields). Following injections of the anterograde tracer biotinylated dextran amine (BDA) into layers 2-5 of each area, labelled axonal varicosities were found ipsilaterally in the other cortical areas. The most prominently labelled pathways were PL-->AId, AId-->PL, IL-->AId/PI, and PI-->IL. Qualitative and quantitative examinations of the laminar distribution of labelled axonal varicosities in the terminal fields indicated the existence of topographically organised 'feed-forward' (insular to PL/IL) and 'feed-back' (PL/IL to insular) pathways. The identity of the post-synaptic targets innervated by the PL/IL to AId pathways were investigated ultrastructurally. An analysis of 250 anterogradely labelled synaptic boutons (taken from layers 2/3) indicated that spine heads (presumed to originate from pyramidal cells) were the principal (88-93%) targets; all identified synaptic junctions were asymmetric. The results define an interconnected network of reciprocal pathways between cortical areas processing general and specific 'viscerosensory' information (AId and PI) and medial areas involved in cognitive (PL) and visceromotor (IL) functions. The data provide important aspects of the cortical circuitry underlying the integration of cognitive and emotional processing mechanisms, not only in rats, but also in primates.     

Life and death signaling pathways contributing to skin cancer

Apoptosis is generally regarded as a critical regulatory event in the development of malignancies in several different organ systems (Thompson, 1995). Initially, oncologists focused on alterations in rates of proliferation and cell cycle kinetics, but more recently an emphasis on apoptosis has dominated the fight against cancer (Evan and Vousden, 2001). As approximately 1,000,000 individuals in the U.S.A. develop skin cancer each year, it is important to elucidate the molecular mechanisms that govern cell survival and cell death in the epidermis (Miller and Weinstock, 1994). Moreover, given that most skin cancers occur on sun-exposed skin, the pro-apoptotic and antiapoptotic response of keratinocytes (KC) to UV light is of particular relevance to the development of skin cancer (Brash et al, 1996). Whereas both squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) arise from epidermal KC, it is becoming increasingly apparent that the natural history of their development, their underlying molecular pathogenesis, and potential involvement of antiapoptotic pathways are significantly different. Nonetheless, as pointed out later in the text, significant progress is being made in our understanding of the pathophysiology of these relatively common epithelial-cell-derived neoplasms. In this review we will explore four topics: first, a review of the life and death signaling pathways operative in normal human skin that prevents premature apoptosis of KC with an emphasis on nuclear factor kappaB (NFkappaB) survival signals; second, the molecular pathways that are engaged and regulate apoptosis after normal KC are exposed to ultraviolet (UV) light; third, the apoptotic resistant mechanisms that premalignant and malignant KC utilize to avoid cell death; fourth, therapeutic strategies that can render malignant cells more susceptible to apoptosis with an emphasis on a death pathway mediated by the death ligand TRAIL.