Neuroendocrine and behavioral effects of embryonic exposure to endocrine disrupting chemicals in birds

Endocrine disrupting chemicals (EDCs) exert hormone-like activity in vertebrates and exposure to these compounds may induce both short- and long-term deleterious effects including functional alterations that contribute to decreased reproduction and fitness. An overview of the effects of a number of EDCs, including androgenic and estrogenic compounds, will be considered. Many studies have been conducted in the precocial Japanese quail, which provides an excellent avian model for testing these compounds. Long-term impacts have also been studied by raising a subset of animals through maturation. The EDCs examined included estradiol, androgen active compounds, soy phytoestrogens, and atrazine. Effects on behavior and hypothalamic neuroendocrine systems were examined. All EDCs impaired reproduction, regardless of potential mechanism of action. Male sexual behavior proved to be a sensitive index of EDC exposure and embryonic exposure to a variety of EDCs consistently resulted in impaired male sexual behavior. Several hypothalamic neural systems proved to be EDC responsive, including arginine vasotocin (VT), catecholamines, and gonadotropin releasing hormone system (GnRH-I). Finally, EDCs are known to impact both the immune and thyroid systems; these effects are significant for assessing the overall impact of EDCs on the fitness of avian populations. Therefore, exposure to EDCs during embryonic development has consequences beyond impaired function of the reproductive axis. In conclusion, behavioral alterations have the advantage of revealing both direct and indirect effects of exposure to an EDC and in some cases can provide a valuable clue into functional deficits at different physiological levels.     

Somatostatin receptor (SSTR) subtype-selective analogues differentially suppress in vitro growth hormone and prolactin in human pituitary adenomas. Novel potential therapy for functional pituitary tumors.

Previously, we have shown somatostatin receptor (SSTR) subtype-specific regulation of growth hormone (GH), thyroid-stimulating hormone, and prolactin (PRL) secretion in human fetal pituitary cultures, where GH and thyroid-stimulating hormone are mediated by both SSTR2 and SSTR5, whereas SSTR2 preferentially mediates PRL secretion. We now tested SSTR subtype-selective analogues in primary human GH- and PRL-secreting pituitary adenoma cultures. Analogue affinities determined by membrane radioligand binding in cells stably expressing human SSTR forms were either SSTR2 or SSTR5-selective. Analogues preferential either for SSTR2, including octreotide, lanreotide, and novel compounds with improved affinity for SSTR2, or new SSTR5-selective compounds suppressed GH in tumor cell cultures (up to 44% of control; P < 0.0005). However, novel analogues from both groups were 30-40% more potent than octreotide and lanreotide in suppressing GH (P < 0.05). Heterologous analogue combinations containing both SSTR2- and SSTR5-selective compounds were more potent in decreasing GH than analogues used alone (P < 0.05), or than combinations of compounds specific for the same receptor subtype (P < 0.005). In contrast, SSTR2-selective analogues did not suppress PRL release from six cultured prolactinomas studied. However, new SSTR5-selective analogues suppressed in vitro PRL secretion (30-40%; P < 0.05) in four of six prolactinomas. These results suggest that both SSTR2 and SSTR5 are involved in GH regulation in somatotroph adenoma cells, whereas SSTR5 exclusively regulates PRL secretion from prolactinoma cells. Thus, somatostatin analogues with improved selective binding affinity for these receptor subtypes may be effective in the treatment of either GH- or PRL-secreting adenomas.     

Somatostatin analogs in vitro effects in a growth hormone-releasing hormone-secreting bronchial carcinoid

A 29-yr-old woman presented with acromegaly, pituitary gland enlargement, and an isolated pulmonary mass of 3.3 cm in diameter, which displayed a very high tracer uptake after OctreoScan. Plasma GHRH levels were markedly elevated. The patient underwent left lung upper lobectomy, and histopathology disclosed a bronchial atypical carcinoid. The tissue was examined for somatostatin (SRIH) receptor subtypes (SSTRs) 1-5 expression by RT-PCR. Cultured tumor cells were treated with SRIH, lanreotide (BIM-23014), or SRIH analogs selective for SSTR2 (BIM-23120), SSTR5 (BIM-23206), or SSTR1 (BIM-23926). GHRH was measured in the medium after 6 h, and cell viability was assessed after 48 h. RT-PCR analysis showed expression of SSTR1, -2, and -5. GHRH secretion was significantly reduced by SRIH (-50%), Lan (-35%), as well as by the SSTR2, SSTR5, and SSTR1 selective agonists (-55, -75, and -20%, respectively), whereas cell viability was not affected. Our data show SSTR expression in a GHRH-secreting bronchial carcinoid and provide evidence that, in vitro, selective SSTR activation differently inhibit ectopic GHRH secretion. These findings suggest that SSTR-specific SRIH analogs may be useful in the medical therapy of GHRH-secreting bronchial carcinoids.     

The influence of diabetes mellitus on the practice and outcomes of percutaneous coronary intervention in the community: a report from the HCA database

BACKGROUND: Diabetics remain a high-risk group for those undergoing percutaneous coronary intervention (PCI) using balloon angioplasty and/or intracoronary stents for myocardial revascularization. The objective of this study is to compare clinical characteristics, demographics, procedure indications, lesion characteristics, and acute and long-term outcomes between diabetic patients and non-diabetic patients in a community based PCI registry. METHODS AND RESULTS: Information on patient demographics, coronary risk factors, lesion characteristics, procedures, and outcomes were derived from an HCA, Inc. database on all patients undergoing a PCI procedure in one of four community cardiac catheterization laboratories (CCL). A total of 3,139 patients who underwent PCI procedures from July 1, 1999 through September 30, 2000 were enrolled in this study. Approximately one-third of these patients completed a follow-up survey one year after their initial encounter. Analysis was limited to those patients undergoing PCI of native vessels with stents or conventional balloon angioplasty; patients with target lesions in bypass grafts or those treated with atherectomy were excluded. Approximately 23.5% of the patients enrolled in the study were diabetic. This study found no significant difference in any acute outcome between diabetic and non-diabetic patients in the hospital episode associated with the index PCI procedure. However, data from the 1-year follow-up survey indicates diabetic patients tended to have more target lesion revascularization (TLR) (13.6% versus 8.9%; p = 0.07) and more target vessel revascularization (TVR) (17.6% versus 12.7%; p = 0.058) than non-diabetic patients. In addition, adjusted odds ratios indicate that diabetic patients were 1.6 times more likely to have a second PCI procedure in another vessel (p = 0.013), 2.4 times more likely to undergo bypass surgery (p = 0.003), 1.9 times more likely to undergo an additional revascularization procedure (p < 0.001) and 1.8 times more likely to experience any major adverse cardiac events (p < 0.001) than non-diabetic patients during the follow-up period. CONCLUSIONS: This study indicates that selected diabetic patients can be treated for myocardial revascularization using PCI procedures with acceptable acute outcomes. However, diabetic patients undergoing PCIs have significantly more disease progression and are more likely to experience the need for recurrent revascularization.     

Emerging arboviruses and implications for pediatric transplantation: A review

Recent years have brought a rise in newly emergent viral infections, primarily in the form of previously known arthropod‐transmitted viruses that have increased significantly in both incidence and geographical range. Of particular note are DENV, CHIKV, and ZIKV, which are transmitted mostly by Aedes species of mosquitoes that exhibit a wide and increasing global distribution. Being important pathogens for the general population, these viruses have the potential to be devastating in the international transplant community, with graft rejection and death as possible outcomes of infection. In this review, we discuss the current state of knowledge for these viruses as well as repercussions of infection in the solid organ and HSCT population, with a focus, when possible, on pediatric patients.     

Growth hormone deficiency in the Rothmund-Thomson syndrome

We describe the first proven occurrence of growth hormone deficiency in an individual with the Rothmund-Thomson syndrome. This was suspected because of the patient's severely retarded growth and bone age and her failure to respond normally to growth hormone stimulation testing with l-DOPA, arginine, and growth hormone releasing factor. In addition, we have briefly reviewed other genetic and malformation syndromes that have been found associated with growth hormone deficiency. We recommend that growth hormone deficiency be considered in these syndromes, especially when the growth failure is more marked than expected.