Juvenile granulosa cell tumour of the ovary presenting with hyperprolactinaemic amenorrhoea and galactorrhoea

Secondary amenorrhoea and galactorrhoea represent a common endocrine presentation. We report a case of an oestrogen-producing juvenile granulosa cell tumour (JGCT) of the ovary in a 16-year-old post-pubertal woman with hyperprolactinaemia amenorrhoea and galactorrhoea which resolved following surgical resection of the tumour. This patient presented with a 9-month history of secondary amenorrhoea and a 2-month history of galactorrhoea. Elevated serum prolactin at 7081 mIU/l and suppressed gonadotropins (LH <0.1 U/l; FSH <0.1 U/l) were detected. Serum oestradiol was significantly elevated at 7442 pmol/l with undetectable β-human chorionic gonadotropin. MRI showed a bulky pituitary with no visible adenoma. MRI of the abdomen showed a 4.8 cm mass arising from the right ovary with no evidence of metastatic disease. Serum inhibin B was elevated at 2735 ng/l. A right salpingo-oophorectomy was performed, and histology confirmed the diagnosis of a JGCT, stage International Federation of Gynaecology and Obstetrics 1A. Immunohistochemical staining for prolactin was negative. Post-operatively, oestrogen and prolactin levels were normalised, and she subsequently had a successful pregnancy. In summary, we present a case of an oestrogen-secreting JGCT with hyperprolactinaemia manifesting clinically with galactorrhoea and secondary amenorrhoea. We postulate that observed hyperprolactinaemia was caused by oestrogenic stimulation of pituitary lactotroph cells, a biochemical state analogous to pregnancy. To the best of our knowledge, this is the first report of hyperprolactinaemia as a result of excessive oestrogen production in the context of a JGCT. LEARNING POINTS: Hyperprolactinaemia with bilateral galactorrhoea and secondary amenorrhoea has a wide differential diagnosis and is not always caused by a prolactin secreting pituitary adenoma.Significantly elevated serum oestradiol levels in the range seen in this case, in the absence of pregnancy, are indicative of an oestrogen-secreting tumour.JGCTs are rare hormonally active ovarian neoplasms mostly secreting steroid hormones.Serum inhibin can be used as a granulosa cell-specific tumour marker.JGCTs have an excellent prognosis in the early stages of the disease

Screening of biocatalysts for synthesis of the Wieland-Miescher ketone.

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly citedLipases, a versatile class of biocatalysts, have been shown to function in non-aqueous media/organic solvents and to possess “promiscuous� catalytic activity for a wide range of organic transformations. In this study, we explored the biocatalytic properties of a library of commercially available lipases by screening them for catalysis of a one-pot synthesis of Wieland–Miescher ketone, an important intermediate in the synthesis of biologically active compounds such as steroids and terpenoids, from methyl vinyl ketone and 2-methyl-1,3-cyclohexanedione. As a direct outgrowth of this screen, we created an optimized procedure for Wieland–Miescher ketone (WMK) synthesis using crude lipase preparations, characterizing both reaction yield and enantiomeric excess. We also identified principal components of the crude lipase mixture through proteomics and present evidence for a non-lipolytic origin of the observed catalysis. Finally, using the optimized conditions developed in this study, we propose a general absorbance-based screening methodology for assessing biocatalytic potential of crude enzyme preparations for synthesis of WMK.ECU Open Access Publishing Support Fun

Viral expression and molecular profiling in liver tissue versus microdissected hepatocytes in hepatitis B virus - associated hepatocellular carcinoma.

Background: The molecular mechanisms whereby hepatitis B virus (HBV) induces hepatocellular carcinoma (HCC) remain elusive. We used genomic and molecular techniques to investigate host-virus interactions by studying multiple areas of the same liver from patients with HCC. Methods: We compared the gene signature of whole liver tissue (WLT) versus laser capture-microdissected (LCM) hepatocytes along with the intrahepatic expression of HBV. Gene expression profiling was performed on up to 17 WLT specimens obtained at various distances from the tumor center from individual livers of 11 patients with HCC and on selected LCM samples. HBV markers in liver and serum were determined by real-time polymerase chain reaction (PCR)and confocal immunofluorescence. Results: Analysis of 5 areas of the liver showed a sharp change in gene expression between the immediate perilesional area and tumor periphery that correlated with a significant decrease in the intrahepatic expression of HB surface antigen (HBsAg). The tumor was characterized by a large preponderance of down-regulated genes, mostly involved in the metabolism of lipids and fatty acids, glucose, amino acids and drugs, with down-regulation of pathways involved in the activation of PXR/RXR and PPARα/RXRα nuclear receptors, comprising PGC-1α and FOXO1, two key regulators critically involved not only in the metabolic functions of the liver but also in the life cycle of HBV, acting as essential transcription factors for viral gene expression. These findings were confirmed by gene expression of microdissected hepatocytes. Moreover, LCM of malignant hepatocytes also revealed up-regulation of unique genes associated with cancer and signaling Pathways, including two novel HCC-associated cancer testis antigen genes, NUF2 and TTK. Conclusions: Integrated gene expression profiling of whole liver tissue with that of microdissected hepatocytes demonstrated that HBV-associated HCC is characterized by a metabolism switch-off and by a significant reduction in HBsAg. LCM proved to be a critical tool to validate gene signatures associated with HCC and to identify genes that may play a role in hepatocarcinogenesis, opening new perspectives for the discovery of novel diagnostic markers and therapeutic targets

Effects of Exogenous Antioxidants on Dietary Iron Overload

In dietary iron overload, excess hepatic iron promotes liver damage. The aim was to attenuate free radical-induced liver damage using vitamins. Four groups of 60 Wistar rats were studied: group 1 (control) was fed normal diet, group 2 (Fe) 2.5% pentacarbonyl iron (CI) followed by 0.5% Ferrocene, group 3 (Fe + V gp) CI, Ferrocene, plus vitamins A and E (42× and 10× RDA, respectively), group 4 (Fe – V gp) CI, Ferrocene diet, minus vitamins A and E. At 20 months, glutathione peroxidase (GPx), superoxide dismutase (SOD), Oxygen Radical Absorbance Capacity (ORAC), Ames mutagenicity test, AST, ALT and 4-hydroxynonenal (4-HNE) immunohistochemistry were measured. 8OHdG levels of the Fe + V and Fe – V groups were 346 ± 117 and 455 ± 151, ng/g w.wt, respectively. Fe + V and Fe – V differences were significant (p<0.005). A positive correlation between DNA damage and mutagenesis existed (p<0.005) within the iron-fed gps. AST levels for Fe + V and Fe – V groups were 134.6 ± 48.6 IU and 202.2 ± 50.5 IU, respectively. Similarly, ALT levels were 234.6 ± 48.3 IU and 329.0 ± 48.6 IU, respectively. However, Fe – V and Fe + V groups transaminases were statistically insignificant. 4-HNE was detected in Fe + V and Fe – V gp livers. Vitamins A and E could not prevent hepatic damage

Response of low-strength phenol-acclimated activated sludge to shock loading of high phenol concentrations

(ii) investigate the degradation pathways and (iii) model the growth and biodegradation kinetics, all under the condition of increasingly higher phenol concentrations (step-up shock loading). With the use of activated sludge acclimated to phenol concentration of 140 mg∙ℓ−1 (low-strength phenol-acclimated activated sludge), complete degradation of phenol with a COD removal efficiency of more than 95% was achieved up to 1 050 mg∙ℓ−1 of initial phenol concentration. At low initial phenol concentrations, the experimental results were indicative of the meta-cleavage pathway for phenol degradation. When the initial phenol concentration was above 630 mg∙ℓ−1, the degradation results were indicative of both meta- and ortho-cleavage pathways. The values of the Haldane kinetic parameters indicated a low degree of inhibition exerted by the presence of increasing phenol concentration. This was substantiated by the observation that the rate constant of phenol removal decreased by only 33% even though the initial phenol concentration was increased by 15 times from 70 to 1 050 mg∙ℓ−1.Thus, the activated sludge acclimated to only 140 mg∙ℓ−1 of phenol could successfully treat up to 1 050 mg∙ℓ−1 of phenol without experiencing complete inhibition during the degradation process.Keywords: Phenol removal, low-strength phenol-acclimated activated sludge, degradation pathway, Haldane kinetic paramete

Structural Progression in Patients with Definite and Non-Definite Arrhythmogenic Right Ventricular Cardiomyopathy and Risk of Major Adverse Cardiac Events

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare inherited disease characterised by early arrhythmias and structural changes. Still, there are limited echocardiography data on its structural progression. We studied structural progression and its impact on the occurrence of major adverse cardiovascular events (MACE). In this single-centre observational cohort study, structural progression was defined as the development of new major or minor imaging 2010 Task Force Criteria during follow-up. Of 101 patients, a definite diagnosis of ARVC was made in 51 patients, while non-definite ‘early’ disease was diagnosed in 50 patients. During 4 years of follow-up (IQR: 2–6), 23 (45%) patients with a definite diagnosis developed structural progression while only 1 patient in the non-definite (early) group gained minor imaging Task Force Criteria. Male gender was strongly associated with structural progression (62% of males progressed structurally, while 88% of females remained stable). Patients with structural progression were at higher risk of MACE (64% of patients with MACE had structural progression). Therefore, the rate of structural progression is an essential factor to be considered in ARVC studies

Evaluation of expression and function of the H+/myo-inositol transporter HMIT;

BACKGROUND: The phosphoinositide (PIns) signalling pathway regulates a series of neuronal processes, such as neurotransmitter release, that are thought to be altered in mood disorders. Furthermore, mood-stabilising drugs have been shown to inhibit key enzymes that regulate PIns production and alter neuronal growth cone morphology in an inositol-reversible manner. Here, we describe analyses of expression and function of the recently identified H+/myo-inositol transporter (HMIT) investigated as a potential regulator of PIns signalling. RESULTS: We show that HMIT is primarily a neuronal transporter widely expressed in the rat and human brain, with particularly high levels in the hippocampus and cortex, as shown by immunohistochemistry. The transporter is localised at the Golgi apparatus in primary cultured neurones. No HMIT-mediated electrophysiological responses were detected in rat brain neurones or slices; in addition, inositol transport and homeostasis were unaffected in HMIT targeted null-mutant mice. CONCLUSION: Together, these data do not support a role for HMIT as a neuronal plasma membrane inositol transporter, as previously proposed. However, we observed that HMIT can transport inositol triphosphate, indicating unanticipated intracellular functions for this transporter that may be relevant to mood control