The orexins (hypocretins) have recently been implicated in neurodegeneration associated with narcolepsy. Therefore, the current study was designed to investigate changes in the expression of prepro-orexin and the orexin receptors, OX1R and OX2R following permanent middle cerebral artery occlusion (MCAO) in the rat. Six and twenty-four hours following MCAO, increased OX1R mRNA and protein expression (as assessed by Western blotting and immunohistochemistry) was detected in the ischaemic cortex compared with control tissue. In contrast, however, no increase in OX2R mRNA was detected at any time-point and prepro-orexin levels in the cortex were below assay detection levels. This study shows that orexin receptor localization is altered following cerebral ischaemia. The development of selective orexin receptor antagonists will be crucial in establishing a role for this family of novel peptides in the mechanisms underlying ischaemic cell death.

A program is underway at the Stanford Synchrotron Radiation Laboratory to evaluate at minimally invasive method of visualizing the coronary arteries in man using synchrotron radiation. The design of an X-ray imaging system to accomodate a newly-available X-ray beam 12.3 cm in width is described. The system performance as revealed with test images of phantoms and excised hearts is indicated, and the system components to be tested before clinical studies can begin are identified.

Coronary arteriograms are the clinical reference standard for assessing the status of coronary atherosclerosis. Because of the low sensitivity of conventional x-ray systems to contrast agents, the angiographic procedure requires the direct injection of the contrast agent into the coronary arteries. The hazards and expense associated with arterial invasion severely restrict the use of this method and have led to development of the presènt transvenous approach.1–3

WE1 have recently had an opportunity of confirming, in a case of familial methæmoglobinæmia, the shift to the left in the oxygen dissociation curve of hæmoglobin which Darling and Roughton2 found in hæmoglobin – methæmoglobin mixtures. They suggest that the shift in the curve may be explained by the existence of intermediate compounds, the affinity of which for oxygen is greater than that of hæmoglobin. On this assumption, the formation of methæmoglobin from hæmoglobin does not take place in a single step; but the four iron atoms of the hæmoglobin molecule may be oxidized separately and successively. If the iron in the hæmoglobin (or oxyhæmoglobin) molecule is represented as (Fe++)4, the iron in the intermediate mixed molecules would be (Fe+++) (Fe++)3, (Fe+++)2 (Fe++)2, (Fe+++)3 (Fe++), and that in methæmoglobin itself (Fe+++)4. As the shift in the dissociation curve is fairly large, it is evident that quite appreciable amounts of the intermediate compounds would be present in methæmoglobin – hæmoglobin mixtures, and might afford spectroscopic evidence of their presence. Apart from its theoretical interest, the question is of some practical importance, for alterations in the absorption spectrum due to this cause Would necessitate modifications in the estimation of blood methæmoglobin made by optical methods, for example, that of Evelyn and Malloy3.