Adrenocorticotropin and cortisol hyperresponsiveness to hexarelin in patients with Cushing's disease bearing a pituitary microadenoma, but not in those with macroadenoma

We previously reported that in Cushing's disease (CD) the ACTH- and cortisol (F)-releasing activity of Hexarelin (HEX), a GH secretagogue, is exaggerated with respect to that in normal subjects and is higher than that of human CRH (hCRH), but it is absent in Cushing's syndrome. Our aim was to extend the study about the effects of HEX (2.0 microg/kg, iv) on ACTH and F secretion in 21 patients with CD (3 men and 18 women, 16-68 yr old). Based on magnetic resonance imaging, 15 CD patients had pituitary microadenoma, and 6 had macroadenoma. The results in CD patients were compared with those in 27 normal age-matched controls (NS; 10 men and 17 women, 24-69 yr old). Basal ACTH and F levels in CD were similar in patients with microadenom (mean+/-SEM, 78.3+/-7.2 pg/mL and 237.1+/-23.6 microg/L, respectively) and macroadenoma (57.4+/-9.0 pg/mL and 196.9+/-20.1 microg/L, respectively) and were higher (P < 0.001) than those in NS (17.7+/-2.0 pg/mL and 115.3+/-6.7 microg/L, respectively). In microadenoma CD patients, HEX induced marked ACTH and F increases (delta peak, mean+/-SEM: 261.2+/-77.6 pg/mL and 226.1+/-87.2 microg/L, respectively), which were higher (P < 0.04) than those induced by hCRH (45.6+/-16.9 pg/mL and 84.6+/-25.7 microg/L, respectively). Moreover, in microadenoma CD patients, the ACTH and F responses to HEX were higher (P < 0.001) than those in NS (18.5+/-4.0 pg/mL and 36.1+/-6.8 microg/L, respectively). In macroadenoma CD patients, HEX induced a slight, but significant increase (P < 0.02) in ACTH and F levels (33.9+/-18.0 pg/mL and 89.6+/-34.3 microg/L, respectively), which was not significantly different from that elicited by hCRH (20.0+/-7.0 pg/mL and 54.8+/-21.3 microg/L, respectively). In macroadenoma CD patients, the ACTH and F responses to HEX and hCRH were, in turn, similar to those in NS. In conclusion, our findings demonstrate that the ACTH and F hyperresponsiveness to HEX is present in Cushing's disease with micro-, but not macro- ACTH-secreting pituitary adenoma. This finding agrees with other evidence pointing toward differences in the hormonal behavior between micro- and ACTH-secreting pituitary macroadenomas.     

Quantitative Magneto-Optical Imaging of Supercurrents in Heavy-Ion Irradiated Cuprate and Pnictide Superconductors

Spatial distributions of magnetic field and of current density in superconductors are obtained, in real-time, by the magneto-optical imaging technique with an indicator film. Quantitative values of the local magnetic field and then of the local current density were achieved by a careful optical calibration and custom algorithms for the inversion of Biot–Savart law. An iterative procedure was developed for the correction of artifacts due to the coupling of the indicator film magnetization with the in-plane magnetic field generated by the superconducting sample. This technique is highly valuable when the sample under study has nonuniform properties. Several cases of such systems are shown. Particular attention is devoted to the local variation of structural and chemical properties by means of heavy-ion irradiation. A comparative study of swift-ion irradiation effects between cuprate and pnictide superconductors is addressed. For the case of cuprate materials, some successful applications of the heavy ion irradiation engineering are presented and discussed.     

Influence of galanin and serotonin on the endocrine response to Hexarelin, a synthetic peptidyl GH-secretagogue, in normal women

BACKGROUND: Lack of information about the effect of insurance coverage on the demand for and use of smoking-cessation services has prevented widescale adoption of coverage for such services. METHODS: In a longitudinal, natural experiment, we compared the use and cost effectiveness of three forms of coverage with those of a standard form of coverage for smoking-cessation services that included a behavioral program and nicotine-replacement therapy. The study involved seven employers and a total of 90,005 adult enrollees. The standard plan offered 50 percent coverage of the behavioral program and full coverage of nicotine-replacement therapy. The other plans offered 50 percent coverage of both the behavioral program and nicotine-replacement therapy (reduced coverage), full coverage of the behavioral program and 50 percent coverage of nicotine-replacement therapy (flipped coverage), or full coverage of both the behavioral program and nicotine-replacement therapy. RESULTS: Estimated annual rates of use of smoking-cessation services ranged from 2.4 percent (among smokers with reduced coverage) to 10 percent (among those with full coverage). Smoking-cessation rates ranged from 28 percent (among users with full coverage) to 38 percent (among those with standard coverage). The estimated percentage of all smokers who would quit smoking per year as a result of using the services ranged from 0.7 percent (with reduced coverage) to 2.8 percent (with full coverage). The average cost to the health plan per user who quit smoking ranged from $797 (with standard coverage) to $1,171 (with full coverage). The annual cost per smoker ranged from $6 (with reduced coverage) to $33 (with full coverage). The annual cost per enrollee ranged from $0.89 (with reduced coverage) to $4.92 (with full coverage). CONCLUSIONS: Use of smoking-cessation services varies according to the extent of coverage, with the highest rates of use among smokers with full coverage. Although the rate of smoking cessation among the benefit users with full coverage was lower than the rates among users with plans requiring copayments, the effect on the overall prevalence of smoking was greater with full coverage than with the cost-sharing plans.     

Influence of Irradiation-Induced Correlated and Random Disorder on Flux Pinning in Bulk YBCO Melt-Textured Samples

YBCO melt textured samples were studied after Au ion irradiation of two opposite surface layers of the samples and after proton irradiation. The scaling behavior of the pinning force was studied in order to get information about mechanisms responsible for pinning in the studied samples. Correlated disorder introduced bysurface ion irradiation is effective at high reduced temperatures and leads to the occurrence of a kink in the irreversibility line and to the shift of this line toward higher fields and temperatures. Enhancement of critical current density,increasing with temperature and field, was observed. Random disorder due to proton irradiation does not change the irreversibility line and only provides critical current enhancementdecreasing with temperature and field.     

Galanin positively modulates prolactin secretion in normal women

It is widely accepted that, in man, galanin, a neuropeptide, has a clear GH-releasing effect while its stimulatory influence on PRL secretion is matter of debate. To clarify this point, in 6 normal young women (23-35 yr) in their early follicular phase, we studied the effect of galanin (pGAL, 80 pmol/kg. min infused i.v. over 60 min) on both basal and arginine (ARG, 0.5 g/kg i.v. in 30 min), TRH (400 micrograms i.v. as a bolus at 0 min) or metoclopramide (MCP, 10 mg i.v. as a bolus at 0 min)-stimulated PRL secretion. GAL infusion failed to significantly increase basal PRL levels (peak vs baseline: 12.2 +/- 3.6 vs 8.7 +/- 1.2 micrograms/L) but counteracted the spontaneous PRL decrease observed during saline infusion (AUC: 1216.6 +/- 282.1 vs 672.0 +/- 94.5 micrograms.min/L; p < 0.05). GAL infusion clearly enhanced the PRL response to TRH (AUC: 5806.3 +/- 743.0 vs 3952.1 +/- 423.9 micrograms.min/L, p < 0.05) and ARG (AUC: 3676.8 +/- 382.6 vs 2638.9 +/- 287.0 micrograms.min/L, p < 0.05), respectively. On the other hand, GAL failed to modify the MCP-induced PRL response (AUC: 15409.5 +/- 2085.3 vs 14,787.9 +/- 2045.5 micrograms.min/L). The PRL response to MCP was higher than that to TRH (p < 0.01) which, in turn, was higher than that to ARG (p < 0.01). During GAL infusion, the PRL response to TRH or ARG remained lower (p < 0.01) than that after MCP administration. Thus, in conclusion, present data demonstrate that in normal women galanin enhances the PRL response to ARG and TRH but fails to modify that induced by dopamine receptor blockade with metoclopramide. Based on evidence that the inhibition of central dopaminergic activity inhibits the lactotrope responsiveness to dopaminergic antagonists or TRH, it is unlikely that galanin influences PRL secretion via inhibition of dopaminergic tone.     

Extrinsic defect implantation in sintered YBCO slabs: Magnetic and transport properties

This paper deals with proton irradiation effects on the intragrain and intergrain magnetic and transport properties of sintered YBCO. We have irradiated slab-shaped samples with beams at different fluences and energies, aiming at checking the possibility to modify in a planned way critical currents by means of proton implantation. Magnetic characterizations show enhanced intragrain pinning. Emphasis is given to the possibility to modulate intergrain magnetic properties by irradiation, determining critical current enhancement in optimal field and temperature ranges. Resistive measurements were performed in order to investigate the complex transport phenomena in polycrystalline materials, where superconducting and normal conduction mechanisms coexist. Irradiation-induced effects on both superconducting and normal state resistivity are studied. The addition of extrinsic defects leads to enhanced transport properties, emerging especially when a magnetic field is applied.     

Sr-containing hydroxyapatite: morphologies of HA crystals and bioactivity on osteoblast cells

A series of Sr-substituted hydroxyapatites (HA), of general formula Ca_(10 ? x)Sr_x(PO₄)₆(OH)₂, where x = 2 and 4, were synthesized by solid state methods and characterized extensively. The reactivity of these materials in cell culture medium was evaluated, and the behavior towards MG-63 osteoblast cells (in terms of cytotoxicity and proliferation assays) was studied. Future in vivo studies will give further insights into the behavior of the materials.A paper by Lagergren et al. (1975), concerning Sr-substituted HA prepared by a solid state method, reports that the presence of Sr in the apatite composition strongly influences the apatite diffraction patterns. Zeglinsky et al. (2012) investigated Sr-substituted HA by ab initio methods and Rietveld analyses and reported changes in the HA unit cell volume and shape due to the Sr addition.To further clarify the role played by the addition of Sr on the physico-chemical properties of these materials we prepared Sr-substituted HA compositions by a solid state method, using different reagents, thermal treatments and a multi-technique approach. Our results indicated that the introduction of Sr at the levels considered here does influence the structure of HA. There is also evidence of a decrease in the crystallinity degree of the materials upon Sr addition. The introduction of increasing amounts of Sr into the HA composition causes a decrease in the specific surface area and an enrichment of Sr-apatite phase at the surface of the samples. Bioactivity tests show that the presence of Sr causes changes in particle size and/or morphology during soaking in MEM solution; on the contrary the morphology of pure HA does not change after 14 days of reaction. The presence of Sr, as Sr-substituted HA and SrCl_2, in cultures of human MG-63 osteoblasts did not produce any cytotoxic effect. In fact, Sr-substituted HA increased the proliferation of osteoblast cells and enhanced cell differentiation: Sr in HA has a positive effect on MG-63 cells. In contrast, Sr ions alone, at the concentrations released by Sr-HA (1.21–3.24 ppm), influenced neither cell proliferation nor differentiation. Thus the positive effects of Sr in Sr-HA materials are probably due to the co-action of other ions such as Ca and P.     

A new apparatus for deep patterning of beam sensitive targets by means of high-energy ion beam

The paper reports on a high precision equipment designed to modify over 3-dimensions (3D) by means of high-energy heavy ions the local properties of thin and thick films. A target-moving system aimed at creating patterns across the volume is driven by an x–y writing protocol that allows one to modify beam sensitive samples over micrometer-size regions of whatever shape. The moving system has a mechanical resolution of 15 nm. The issue of the local fluence measurement has been particularly addressed. The setup has been checked by means of different geometries patterned on beam sensitive sheets as well as on superconducting materials. In the last case the 3D modification consists of amorphous nanostructures. The nanostructures create zones with different dissipative properties with respect to the virgin regions. The main analysis method consists of magneto-optical imaging that provides local information on the electrodynamics of the modified zones. Features typical of non-linear current flow hint at which pattern geometry is more functional to applications in the framework of confined nanostructuring of superconducting films.     

Novel and Selective Fluorescent σ2‐Receptor Ligand with a 3,4‐Dihydroisoquinolin‐1‐one Scaffold: A Tool to Study σ2 Receptors in Living Cells

Although sigma‐2 (σ₂) receptors are still enigmatic proteins, they are promising targets for tumor treatment and diagnosis. With the aim of clarifying their role in oncology, we developed a σ₂‐selective fluorescent tracer (compound 5 ) as a specific tool to study σ₂ receptors. By using flow cytometry with 5 , we performed competition binding studies on three different cell lines where we also detected the content of the σ₂ receptors, avoiding the inconvenient use of radioligands. Comparison with a previously developed mixed σ₁/σ₂ fluorescent tracer ( 1 ) also allowed for the detection of σ₁ receptors within these cells. Results obtained by flow cytometry with tracers 1 and 5 were confirmed by standard methods (western blot for σ₁, and Scatchard analysis for σ₂ receptors). Thus, we have produced powerful new tools for research on the σ whose reliability and adaptability to a number of fluorescence techniques will be useful to elucidate the roles of σ receptors in oncology.     

IGF-I levels in prepubertal and pubertal children with Down syndrome

Medical behavior for intensive examination after colo-rectal cancer screening was examined in comparison with that after stomach cancer screening. Examinees who were positive in colo-rectal or stomach cancer screening, provided by an Occupational Health Organization from April 1993 to March 1994, were monitored for their medical behavior through notifications from physicians. The main results were as follows: 1. The proportion of those with the notification from a physician after colo-rectal cancer screening was half of that after stomach cancer screening. 2. Among those notified the rate of those who undertook intensive examination by the end of 12 weeks after the screening was 79.7% for a colo-rectal site and 87.0% for the stomach. The time interval from the screening to the intensive examination for the colo-rectal site was significantly longer than that for stomach. 3. For colo-rectal cancer screening, the proportion of those with the notification was lower in females than in males, and in those aged less than 50 than in those aged 50 or older. There were no differences in the proportion between those screened at the work site and those at the occupational health service center, and between those positive in the fecal occult blood test and those negative in the test but positive in the health interview. These results indicated, assuming that the probability of the physicians' notification was unrelated to the type of examination, a smaller proportion of the examinees positive in the colo-rectal cancer screening consulted a physician for the intensive examination later than those positive in the stomach cancer screening. It is therefore necessary to make colo-rectal cancer screening effective to establish a collaborating system which effectively facilitates the medical behavior of the screening positives.