Prolactinomas, Cushing's disease and acromegaly: debating the role of medical therapy for secretory pituitary adenomas

Pituitary adenomas are associated with a variety of clinical manifestations resulting from excessive hormone secretion and tumor mass effects, and require a multidisciplinary management approach. This article discusses the treatment modalities for the management of patients with a prolactinoma, Cushing's disease and acromegaly, and summarizes the options for medical therapy in these patients. First-line treatment of prolactinomas is pharmacotherapy with dopamine agonists; recent reports of cardiac valve abnormalities associated with this class of medication in Parkinson's disease has prompted study in hyperprolactinemic populations. Patients with resistance to dopamine agonists may require other treatment. First-line treatment of Cushing's disease is pituitary surgery by a surgeon with experience in this condition. Current medical options for Cushing's disease block adrenal cortisol production, but do not treat the underlying disease. Pituitary-directed medical therapies are now being explored. In several small studies, the dopamine agonist cabergoline normalized urinary free cortisol in some patients. The multi-receptor targeted somatostatin analogue pasireotide (SOM230) shows promise as a pituitary-directed medical therapy in Cushing's disease; further studies will determine its efficacy and safety. Radiation therapy, with medical adrenal blockade while awaiting the effects of radiation, and bilateral adrenalectomy remain standard treatment options for patients not cured with pituitary surgery. In patients with acromegaly, surgery remains the first-line treatment option when the tumor is likely to be completely resected, or for debulking, especially when the tumor is compressing neurovisual structures. Primary therapy with somatostatin analogues has been used in some patients with large extrasellar tumors not amenable to surgical cure, patients at high surgical risk and patients who decline surgery. Pegvisomant is indicated in patients who have not responded to surgery and other medical therapy, although there are regional differences in when it is prescribed. In conclusion, the treatment of patients with pituitary adenomas requires a multidisciplinary approach. Dopamine agonists are an effective first-line medical therapy in most patients with a prolactinoma, and somatostatin analogues can be used as first-line therapy in selected patients with acromegaly. Current medical therapies for Cushing's disease primarily focus on adrenal blockade of cortisol production, although pasireotide and cabergoline show promise as pituitary-directed medical therapy for Cushing's disease; further long-term evaluation of efficacy and safety is important.     

DIVE CHARACTERISTICS OF SATELLITE-MONITORED BLUE WHALES (BALAENOPTERA MUSCULUS) OFF THE CENTRAL CALIFORNIA COAST

Dive habits of four Northeast Pacific blue whales ( Balaenoptera musculus ) were studied using satellite-monitored radio tags. Tags summarized dive-duration data into eight 3-h periods daily. One tag additionally summarized dive depth and time-at-depth information for these same periods. Tracking periods ranged from 0.6 to 12.7 d and provided data for 17 three-hour summary periods, representing 2,007 dives (788 of which provided depth information). Total number of dives during a 3-h summary period ranged from 83 to 128. Seventy-two percent of dives were ≤ 1 min long. All whales spent >94% of their time submerged. Average duration of true dives (dives >1 min) ranged from 4.2 to 7.2 min. Seventy-five percent of depth-monitored dives were to ≤16 m, accounting for 78% of that animal's time. Average depth of dives to >16 m was 105 ± 13 m.     

Bluejay 1.0: genome browsing and comparison with rich customization provision and dynamic resource linking

Background  

The Bluejay genome browser has been developed over several years to address the challenges posed by the ever increasing number of data types as well as the increasing volume of data in genome research. Beginning with a browser capable of rendering views of XML-based genomic information and providing scalable vector graphics output, we have now completed version 1.0 of the system with many additional features. Our development efforts were guided by our observation that biologists who use both gene expression profiling and comparative genomics gain functional insights above and beyond those provided by traditional per-gene analyses.     

Trabecular bone loss in collagen antibody-induced arthritis

IntroductionPostmenopausal women with rheumatoid arthritis (RA) have increased risk of developing osteoporosis due to chronic inflammation and estrogen deprivation. Collagen antibody-induced arthritis (CAIA), an experimental polyarthritis model representing the effector phase of arthritis, is mainly mediated by the innate immune system. Compared to the widely used collagen-induced arthritis model, CAIA is conveniently short and can be used in C57BL/6 mice, enabling studies with knock-out mice. However, the impact on bone of the CAIA model in C57BL/6 mice has not previously been studied. Therefore, the aim of this study was to determine if CAIA can be used to study postmenopausal arthritis-induced osteoporosis.MethodsCAIA was induced by administration of collagen-type II antibodies and lipopolysaccharide to ovariectomized female C57BL/6J mice. Control mice received lipopolysaccharide, but no antibodies. Nine days later, femurs were collected for high-resolution micro-CT and histomorphometry. Serum was used to assess cartilage breakdown and levels of complement. Frequencies of immune cell subsets from bone marrow and lymph nodes were analyzed by flow cytometery.ResultsTrabecular bone mass was decreased and associated with increased number of osteoclasts per bone surface in the CAIA model. Also, the frequency of interleukin-17⁺ cells in lymph nodes was increased in CAIA.ConclusionThe present study show that CAIA, a short reproducible arthritis model that is compatible with C57BL/6 mice, is associated with increased number of osteoclasts and trabecular bone loss.