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Mercuric chloride induces in the Brown-Norway rat a biphasic autoimmune disease characterized initially by linear IgG deposits along the glomerular basement membrane followed later by granular IgG deposition. In the present study, anti-glomerular basement membrane antibodies and immune complex-like material were sequentially assessed in serial serum samples. Both were transiently found at the same period. Glomerular linear IgG deposits were present on day 11 but circulating anti-glomerular basement membrane antibodies were only found later on day 16. Circulating immune complexes were first detectable on day 8 before the earliest granular IgG deposits were first observed in the spleen vessels on day 16. The disappearance of circulating anti-glomerular basement membrane antibodies and of circulating immune complexes, although HgCl2 injections were pursued, is in agreement with the self-limited character of mercuric chloride induced autoimmune disease and suggests the induction of immunosuppressive mechanisms.

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The surface of the large cystic spaces and dilated blood vessels in seven cases of aneurysmal bone cysts was studied. The endothelium of the blood vessels was surrounded by a layer of collagen types IV and V, and the endothelial cells contained factor VIII related antigen demonstrated by the peroxidase anti-peroxidase technique. Some blood vessels were dilated resembling small aneurysmal spaces. The visible surfaces of the aneurysmal spaces were devoid of collagen types IV and V, and of factor VIII related antigen. Ultrastructural analysis of paraffin embedded sections did not show the characteristic fine structural features of endothelium covering the aneurysmal spaces. It is concluded that the large spaces in aneurysmal bone cysts are devoid of basement membranes and endothelial cells. The absence of endothelium may explain the abundance of haemorrhages in these lesions. Immunocytochemical demonstration of endothelial antigen provides a valuable tool for the differential diagnosis between aneurysmal bone cysts and vascular tumours.

It has previously been shown that monolayer cultures derived adherent cells (MDAC), apparently consisting of fibroblasts, macrophages, epithelioid cells, and fat cells, can support long-term stem cell proliferation in vitro. In the present study, the hematopoietic support capability of murine MDAC monolayers was confirmed and the cultured cells further characterized with respect to the following properties: esterase I activity, complement (C3) receptors, IgG (Fc) receptors, colony stimulating activity (csa) production, and collagen synthesis. The cultures were also examined immunohistochemically to localize fibronectin, laminin, and collagen synthesis and to identify the collagen subtypes synthesized. MDAC morphology was as described in previous studies, although fat cells were few in number. It was found that MDAC included some cells with esterase I activity and C3 receptors. Fc receptors were not, however, detected, nor did the cultures produce csa, indicating that mononuclear phagocytes were not present. MDAC synthesized collagen types I and III and also fibronectin. Staining for epithelial basement membrane proteins (collagen types IV and V and laminin) was negative. The results indicate that the vast majority of these cultured MDAC were fibroblasts.

Source of fundingThe study was financially supported by Pantarhei Bioscience Conflict of interestYZ is an employee of Pantarhei Bioscience (PRB), the company developing the Androgen RestoredContraceptive concept for contraception. JMF has no conflict of interest in the course of this study.AP shares expertise as a lecturer, member of advisory boards, and/or consultant, with Bayer, Amgen, Gedeon Richter and Teva/Theramex, without personal gain. JMM has nothing to declare. KC has nothing to declare. BF has received fees and grant support from the following companies (in alphabetic order); Andromed, Ardana, Euroscreen, Ferring, Genovum, Merck (MSD), Merck Serono, Organon, Ovascience, Pantharei Bioscience, PregLem, Schering, Schering Plough, Serono, Uteron Pharma, Watson Pharmaceuticals and Wyeth. HCB is the CEO and a shareholder of PRB.After publication of the paper, PRB will make the clinical study report available upon request. The authors alone are responsible for the content and the writing of the paper. Clinical Trial Registration Number: ISRCTN06414473A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT AbstractObjectives: Combined oral contraceptives (COCs) decrease androgen levels, including testosterone (T), which may be associated with sexual dysfunction and mood complaints in some women. We have shown that co-administration of dehydroepiandrosterone (DHEA) to a drospirenone (DRSP) containing COC restored total T levels to baseline and free T levels by 47%. Here we describe the effects on sexual function, mood and quality of life of such an intervention. Study design:This was a randomized, double-blind, placebo-controlled study in 99 healthy COC starters. A COC containing 30 µg ethinylestradiol (EE) and 3 mg DRSP was used for 3 cycles, followed by 6 cycles of the same COC combined with 50 mg/day DHEA or placebo. There were no statistically significant differences between groups for the MSFQ and Q-LES-Q scores. DHEA co-administration resulted in an acceptable safety profile. DHEA negated the beneficial effect of the COC on acne according to the subjects' self-assessment. A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPTConclusions: Co-administration with DHEA did not result in consistent improvements in sexual function, mood and quality of life indicators in women taking EE/DRSP.Retrospectively, the 50 mg dose of DHEA may be too low for this COC.Implications A well-balanced judgment of the clinical consequences of normalizing androgens during COC use may require complete normalization of free T.

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