Persistence of the circadian rhythm of dehydroepiandrosterone in the brain, but not in the plasma, of castrated and adrenalectomized rats

In adrenalectomized and orchidectomized rats, the removal of the steroidogenic endocrine glands is associated with a near-disappearance of corticosterone (B) from plasma and brain; circadian variations of B and of plasma dehydroepiandrosterone (D), characteristic of the intact rat, are no more detected. By contrast, analyses of brain D measurements by the cosinor method demonstrate a persisting circadian rhythm of large amplitude.     

Thermal inactivation and molecular forms of the estrogen receptor: Effects of molybdate

Exposure at 40°C of low salt calf uterine cytosol leads to the “transformation” of the estradiol-receptor complexes in 5 min, immediately followed by the formation of thermostable > 12 S “aggregated” receptor forms. Molybdate prevents this phenomenon but does not reverse it. Molybdate has a protective effect against thermal inactivation of the 9 S non-aggregated form of the receptor in the absence of hormone. In the presence of molybdate, the inactivation rate of this 9 S receptor is the same with and without hormone, and follows a first order reaction ($\text{t}{}_{\mathrm{<mtext>1</mtext><mtext>2</mtext>}}\text{= 7–8 min}$). The biphasic kinetics of thermo-inactivation of estradiol-receptor complexes is ascribable to the relative amounts of non-aggregated and aggregated forms.     

Novel lipoidal derivatives of pregnenolone and dehydroepiandrosterone and absence of their sulfated counterparts in rodent brain

A new sample preparation method coupled to GC-MS analysis was developed and validated for quantification of sulfate esters of pregnenolone (PREG-S) and dehydroepiandrosterone (DHEA-S) in rat brain. Using a solid-phase extraction recycling protocol, the results show that little or no PREG-S and DHEA-S (<1 pmol/g) is present in rat and mouse brain. These data are in agreement with studies in which steroid sulfates were analyzed without deconjugation. We suggest that the discrepancies between analyses with and without deconjugation are caused by internal contamination of brain extract fractions, supposed to contain steroid sulfates, by lipoidal forms of PREG and DHEA (L-PREG and L-DHEA, respectively). These derivatives can be acylated very efficiently with heptafluorobutyric anhydride and triethylamine, and their levels in rodent brain (approximately 1 nmol/g) are much higher than those of their unconjugated counterparts. They are distinct from fatty acid esters, and preliminary data do not favor structures such as sulfolipids or sterol peroxides. Noncovalent interactions between steroids and proteolipidic elements, such as lipoproteins, could account for some experimental data. Given their abundance in rodent brain, the structural characterization and biological functions of L-PREG and L-DHEA in the central nervous system merit considerable attention.     

Comparaison de six méthodes de segmentation du volume tumoral sur la 18F-FDG TEP-TDM avec le volume de référence anatomopathologique dans les cancers bronchopulmonaires non à petites cellules

The ¹⁸F-FDG TEP has demonstrated its importance in oncology, for initial extension and efficacy of antitumoral therapeutics. Several studies have attempted to prove its utility to define tumoral volumes for conformational radiotherapy in nonsmall cell lung cancers. Some authors have suggested the use of threshold of tumor intensity uptake with 40 or 50% of maximal intensity. Black et al. have determined contouring with linear regression formula of mean semi-quantitative index of tumor uptake (standard uptake value): SUV_threshold = 0.307 SUV_average + 0.588. Nestlé et al. have taken into account the background noise intensity and mean intensity of the tumor: I_threshold = β I_average + I_noise with β = 0.15. Our study was done in collaboration with Inserm U618 team and has compared volumes defined on PETscan defined according to different methods based on intensity or SUV to the tumour volume determined on CT scan by radiophysicist. We have compared those volumes with histological volume that we considered for reference. Four patients have been included. They had ¹⁸F-FDG PETscan followed by complete tumoral removal surgery. Specific histological procedure allowed to define complete size of the tumor in reexpanded lung. Comparatively to pathology, the volumes obtained using I_max 40 and I_max 50 are all underestimated. The volumes defined by Black's et al. method are underevaluated for the two largest tumours (15.8% to 22%) and overestimated for the two smallest ones (17.9 to 82.9%). Nestlé's et al. method, using β = 0.15, correctly estimates two tumor volumes over 2 cm, but overestimates the two small tumors (79.6 to 124%). Finally, the corrected Nestlé's et al. formula (using β = 0.264) overestimates three tumours. Volumes defined on CT scan by radiophysicist are correct for one lesion, underestimated for one and overestimated for two other ones (44 and 179.5%). Nestlé's et al. method seems to be the most accurate for tumours over 2 cm of diameter. Today no method can correctly estimate the volume of smaller tumours. To improve those segmentation approaches, partial volume effect correction needs to be implemented for small tumours or tumours close to mediastinal local extension. The main indication of segmentation based on FDG PET is tumour greater than 2 cm for which treatment will be radiotherapy alone or radiotherapy associated with chemotherapy. Our study is important because it compares the different methods described in the literature with the reference histological volume of the tumor, which is the only way to validate tumor segmentation method.