Possible targets for nonimmunosuppressive therapy of Graves' orbitopathy.

CONTEXT: Graves' orbitopathy (GO) is caused by expansion of the orbital contents by excess adipogenesis and overproduction of hyaluronan (HA). Immunosuppressive and antiinflammatory treatments of GO are not always effective and can have side effects, whereas targeting GO-associated tissue remodeling might be a more logical therapeutic strategy. Previously we reported that signaling cascades through IGF1 receptor and thyrotropin receptor within orbital preadipocytes/fibroblasts drove adipogenesis and HA production. Our current study combined the stimulation of IGF1 receptor and thyrotropin receptor increase of HA accumulation, which we hypothesize is by activation of phosphatidylinositol 3-kinase (PI3K)-1A/PI3K1B, respectively. The central aim of this study was to investigate whether PI3K/mammalian target of rapamycin complex 1 (mTORC1) inhibitors affected adipogenesis and/or HA production within orbital preadipocyte/fibroblasts. METHODS: Human orbital preadipocytes were treated with/without inhibitors, LY294002 (PI3K1A/mTORC1), AS-605240 (PI3K1B), or PI103 (PI3K1A/mTORC1) in serum-free medium for 24 hours or cultured in adipogenic medium for 15 days. Quantitative PCR was used to measure hyaluronan synthases (HAS2) transcripts and the terminal adipogenesis differentiation marker lipoprotein lipase. HA accumulation in the medium was measured by an ELISA. RESULTS: Unlike AS-605240, both LY294002 (10 µM) and PI-103 (5 µM) significantly decreased HAS2 transcripts/HA accumulation and adipogenesis. Because PI-103 and LY294002 are dual PI3K/mTOR inhibitors, we investigated the inhibition of mTORC1 (rapamycin 100 nM), which significantly decreased adipogenesis but had no effect on HAS2 transcripts/HA, implicating PI3K-1A in the latter. CONCLUSIONS: The combined inhibition of PI3K1A and mTORC1 signaling in vitro decreased both HA accumulation and adipogenesis. Because PI3K and mTOR inhibitors are clinically used to treat other conditions, they have the potential to be repositioned to be used as an alternative nonimmunosuppressive therapy of GO.

Can citizen science survey non-indigenous fish species in the eastern Mediterranean Sea?

Engaging non-scientists to survey ecosystems, a process known as citizen science has been adopted worldwide. For the first time, this was applied to monitor fish assemblages in the Kas Peninsula, Turkey, an area known for its important Lessepsian fish populations. For 3 years (2004, 2007 and 2010), fish assemblages were surveyed using underwater visual census by transect method. A total of 29 species was observed, seven of which were Lessepsian species. Results show a significant increase in the Lessepsian species over the study period. In 2004, they represented 34% of the total abundance, increasing to >61% in 2010. Differences were observed in the progression of populations between two invasive herbivores, Siganus rivulatus and Siganus luridus (Siganidae), and two native herbivores, Sparisoma cretense (Scaridae) and Sarpa salpa (Sparidae). The siganids were recorded each year in all sites, whereas S. cretense was regularly observed in fewer numbers, while S. salpa was rarely censused. Abundance of Siganus spp. increased threefold in 6 years while abundances of S. cretense and S. salpa remained stable. S. rivulatus was the most abundant among the four species. Its competitive superiority may be due to its greater adaptability to fluctuating environmental conditions and biological traits, e.g. rapid growth, earlier sexual maturity, high fecundity. Because siganids are herbivorous, their presence can strongly impact algal ecosystems. It is then important to follow their spreading at a large scale, but this can be challenging due to the limited number of scientists. Adopting citizen science can thus be a useful strategy to monitor the spread of invasive species in the Mediterranean.

A silent myocardial infarction in the diabetes outpatient clinic: case report and review of the literature.

UNLABELLED: Silent myocardial ischaemia (SMI), defined as objective evidence of myocardial ischaemia in the absence of symptoms, has important clinical implications for the patient with coronary artery disease. We present a dramatic case of SMI in a diabetes patient who attended annual review clinic with ST elevation myocardial infarction. His troponin was normal on admission but raised to 10.7 ng/ml (normal <0.5) when repeated the next day. His angiogram showed diffused coronary artery disease. We here discuss the implications of silent ischaemia for the patient and for the physician caring for patients with diabetes. LEARNING POINTS: Silent myocardial ischaemia (SMI) is an important clinical entity.SMI is common and occurs with increased frequency in patients with diabetes.SMI is an independent predictor of mortality.Recognition may lead to early intervention.

Secondary resistance to cabergoline therapy in a macroprolactinoma: a case report and literature review.

Primary resistance to dopamine agonists occurs in 10-15% of prolactinomas but secondary resistance following initial biochemical and anti-proliferative response is very rare and has only been hitherto described in four previous cases, two with bromocriptine and two with cabergoline. We describe a case of a 57-year-old woman who presented with a large macroprolactinoma with suprasellar extension. She was initially treated with bromocriptine therapy with a resolution of symptoms, marked reduction in prolactin concentration and complete tumour shrinkage; a response which was subsequently maintained on cabergoline. After 8 years of dopamine agonist therapy, her prolactin concentration began to rise and there was symptomatic recurrence of her tumour despite escalating doses of cabergoline up to 6 mg weekly. Non-compliance was outruled by observed inpatient drug administration. The patient underwent surgical debulking followed by radiotherapy with good response. This case adds to the previous two cases of secondary resistance to cabergoline therapy in prolactinomas a marked initial response. While the mechanism of secondary resistance remains unknown and not possible to predict, close observation of prolactinoma patients on treatment is necessary.

Hypoglycaemia in an adult male: a surprising finding in pursuit of insulinoma.

A 50-year-old man who had suffered several episodes of early morning sweats and tremors was diagnosed as having hyperinsulinaemic hypoglycaemia. Cross-sectional imaging and endoscopic ultrasound revealed no pancreatic lesion. A selective intra-arterial calcium infusion study showed a two-fold increase of insulin secretion after infusion of the splenic and superior mesenteric arteries. Laparotomy was performed, no lesion was identified after full mobilisation of the pancreas, and nothing was evident with intra-operative ultrasound. A distal pancreatectomy was performed. Microscopically, the pancreas exhibited diffuse islet cell hyperplasia consistent with nesidioblastosis. The patient remains euglycaemic eight months post-operatively.