Alterations of store-operated calcium entry and cyclopiazonic acid-induced endothelium-derived relaxations in aging rat thoracic aorta

The purpose of our study was to investigate whether endothelium-derived relaxations induced by store depletion are altered in aging rat thoracic aorta. Vascular responses were measured in aortic segments isolated from young (2–4 month) and old (20–24 month) male Sprague-Dawley rats. In phenylephrine-contracted intact tissues, receptor-mediated and receptor-independent endothelium-derived relaxations were induced by acetylcholine (ACh) and sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA) blocker cyclopiazonic acid (CPA), respectively. In addition, CPA-induced changes in intracellular calcium levels were monitored in fura-2-loaded endothelium-denuded tissues. Real-time quantitative reverse transcription polymerase chain reaction and western blot analysis were performed to determine the transient receptor potential canonical (TRPC) 4 mRNA and protein levels. Endothelial TRPC4 mRNA levels were apparently decreased in aging rats. Immunoblot analysis showed that TRPC4 protein levels significantly decreased in intact aorta from 20- to 24-month-old rats compared to that from 2- to 4-month-old rats. ACh- and CPA-induced endothelium-dependent relaxations decreased in old rat aorta without any change in direct vasodilation induced by sodium nitroprusside. Store-operated Ca2+ entry (SOCE) induced by CPA was significantly decreased, whereas sarcoplasmic reticulum Ca2+ release was unaffected in endothelium-denuded aging rat aorta. In conclusion, TRPC4 downregulation could be associated with decreased endothelium-dependent vasorelaxations. As endothelial nitric oxide synthase is activated by SOCE-induced caveolar internalization, tracking the expression levels of SERCA, ion channels, and/or associated proteins involved in SOCE would lead to the development of novel therapeutics for age-related vasospastic disorders with dysfunctional endothelium

Effective Visible Light Exploitation by Copper Molybdo-tungstate Photoanodes

The need for stable oxide-based semiconductors with a narrow band gap, able to maximize the exploitation of the visible light portion of the solar spectrum, is a challenging issue for photoelectrocatalytic (PEC) applications. In the present work, CuW1 12xMoxO4 (Eg = 2.0 eV for x = 0.5), which exhibits a significantly reduced optical band gap Eg compared with isostructural CuWO4 (Eg = 2.3 eV), was investigated as a photoactive material for the preparation of photoanodes. CuW0.5Mo0.5O4 electrodes with different thicknesses (80 12530 nm), prepared by a simple solution-based process in the form of multilayer films, effectively exhibit visible light photoactivity up to 650 nm (i.e., extended compared with CuWO4 photoanodes prepared by the same way). Furthermore, the systematic investigation on the effects on photoactivity of the CuW0.5Mo0.5O4 layer thickness evidenced that long-wavelength photons can better be exploited by thicker electrodes. PEC measurements in the presence of NaNO2, acting as a suitable hole scavenger ensuring enhanced photocurrent generation compared with that of water oxidation while minimizing dark currents, allowed us to elucidate the role that molybdenum incorporation plays on the charge separation efficiency in the bulk and on the charge injection efficiency at the photoanode surface. The adopted Mo for W substitution increases the visible light photoactivity of copper tungstate toward improved exploitation and storage of visible light into chemical energy via photoelectrocatalysis

Minimally invasive treatment of urinary fistulas using n-butyl-2-cyanoacrylate : a valid first option

BACKGROUND: A few single case reports and only one clinical series have been published so far about the use of N-butyl-2-cyanoacrylate in the treatment of urinary fistulas persisting after conventional urinary drainage. CASE PRESENTATION: We treated five patients with a mean age of 59.2 years presenting iatrogenic urinary fistulas which persisted following conventional drainage manouvres. There were 3 calyceal fistulas following open, laparoscopic and robotic removal of renal lesions respectively, one pelvic fistula after orthotopic ileal neobladder and a bilateral dehiscence of uretero-sigmoidostomy. We used open-end catheters of different sizes adopting a retrograde endoscopic approach for cyanoacrylate injection in the renal calyces, while a descending percutaneous approach via the pelvic drain tract and bilateral nephrostomies respectively was used for the pelvic fistulas. Fluoroscopic control was always used during the occlusion procedures. The amount of adhesive injected ranged between 2 and 5 cc and in one case the procedure was repeated. With a median follow-up of 11 months we observed clinical and radiological resolution in 4 cases (80%), while a recurrent and infected calyceal fistula after laparoscopic thermal renal damage during tumor enucleoresection required nephrectomy. No significant complications were documented. CONCLUSIONS: In an attempt to spare further challenging surgery in patients that had been already operated on recently, minimally invasive occlusion of persistent urinary fistulas with N-butyl-2-cyanoacrylate represents a valid first line treatment, justified in cases when the urinary output is not excessive and there is a favorable ratio between the length and diameter of the fistulous tract

Fabrication of Pt/Ti/TiO2 Photoelectrodes by RF-Magnetron Sputtering for Separate Hydrogen and Oxygen Production

Evolution of pure hydrogen and oxygen by photocatalytic water splitting was attained from the opposite sides of a composite Pt/Ti/TiO2 photoelectrode. The TiO2 films were prepared by radio frequency (RF)-Magnetron Sputtering at different deposition time ranging from 1 up to 8 h and then characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM) and ultraviolet-visible-near infrared (UV-vis-NIR) diffuse reflectance spectroscopy. The photocatalytic activity was evaluated by incident photon to current efficiency (IPCE) measurements and by photocatalytic water splitting measurements in a two-compartment cell. The highest H2 production rate was attained with the photoelectrode prepared by 6 h-long TiO2 deposition thanks to its high content in the rutile polymorph, which is active under visible light. By contrast, the photoactivity dropped for longer deposition time, because of the increased probability of electron-hole recombination due to the longer electron transfer path

C-MYC, HIF-1α, ERG, TKT, and GSTP1: an Axis in Prostate Cancer?

To analyze putative biomarkers for prostate cancer (PCA) characterization, the second leading cause of cancer-associated mortality in men. Quantification of the expression level of c-myc and HIF-1α was performed in 72 prostate cancer specimens. A cohort of 497 prostate cancer patients from The Cancer Genome Atlas (TCGA) database was further analyzed, in order to test our hypothesis. We found that high c-myc level was significantly associated with HIF-1α elevated expression (p = 0.008) in our 72 samples. Statistical analysis of 497 TCGA prostate cancer specimens confirmed the strong association (p = 0.0005) of c-myc and HIF-1α expression levels, as we found in our series. Moreover, we found high c-myc levels significantly associated with low Glutatione S-transferase P1 (GSTP1) expression (p = 0.01), with high Transketolase (TKT) expression (p < 0.0001). High TKT levels were found in TCGA samples with low GSTP1 mRNA (p < 0.0001), as shown for c-myc, and with ERG increased expression (p = 0.02). Finally, samples with low GSTP1 expression displayed higher ERG mRNA levels than samples with high GSTP1 score (p < 0.0001), as above shown for c-myc. Our study emphasizes the notion of a potential value of HIF-1α and c-myc as putative biomarkers in prostate cancer; moreover TCGA data analysis showed a putative crosstalk between c-myc, HIF-1α, ERG, TKT, and GSTP1, suggesting a potential use of this axis in prostate cancer

A New MEN2 Syndrome with Clinical Features of Both MEN2A and MEN2B Associated with a New RET Germline Deletion

Background. Multiple endocrine neoplasia type 2 (MEN2) is a hereditary cancer syndrome caused by RET proto-oncogene mutation. Two different clinical variants of MEN2 are known (MEN2A and MEN2B): medullary thyroid carcinoma (MTC) almost always present and associated with pheochromocytoma (Pheo), and primary hyperparathyroidism (HPTH) in MEN2A and with Pheo and other nonendocrine diseases in MEN2B. Case Report. A 7-year-old girl, previously treated for a pelvic plexiform neurofibroma, arrived at our observation with a peculiar MEN2B syndrome and with HPTH. The neck ultrasound showed bilateral thyroid nodules, local lymph node lesions, and a suspicious left hyperplastic parathyroid. The CT scan showed a megacolon and described the persistence of the pelvic tumor. A new RET germline deletion in exon 11 (c.1892_1899delCGAGCT; p.Glu632_Leu633del) was found. She underwent total thyroidectomy, central compartment and latero-cervical lymph node dissection, and neck exploration for primary HPTH. The histology confirmed bilateral MTC, multiple lymph node metastases, a hyperplastic parathyroid, and a parathyroid adenoma. Conclusions. This is the first case of a complex syndrome characterized by peculiar features of MEN2B, without Pheo but with a pelvic plexiform neurofibroma and with HPTH, which is typical of MEN2A. A "de novo"new germline RET deletion located in exon 11 was found

Understanding the nature of "superhard graphite"

Numerous experiments showed that on cold compression graphite transforms into a new superhard and transparent allotrope. Several structures with different topologies have been proposed for this phase. While experimental data are consistent with these models, the only way to solve this puzzle is to find which structure is kinetically easiest to form. Using state-of-the-art molecular-dynamics transition path sampling simulations, we investigate kinetic pathways of the pressure-induced transformation of graphite to various superhard candidate structures. Unlike hitherto applied methods for elucidating nature of superhard graphite, transition path sampling realistically models nucleation events necessary for physically meaningful transformation kinetics. We demonstrate that nucleation mechanism and kinetics lead to $M$-carbon as the final product. $W$-carbon, initially competitor to $M$-carbon, is ruled out by phase growth. Bct-C$_4$ structure is not expected to be produced by cold compression due to less probable nucleation and higher barrier of formation