Protective effect of melatonin against oxidative stress induced by ligature of extra-hepatic biliary duct in rats: comparison with the effect of S-adenosyl-L-methionine

In the present research, we studied the effect of the administration of melatonin or S-adenosyl-L-methionine (S-AMe) on oxidative stress and hepatic cholestasis produced by double ligature of the extra-hepatic biliary duct (LBD) in adult male Wistar rats. Hepatic oxidative stress was evaluated by the changes in the amount of lipid peroxides and by the reduced glutathione content (GSH) in lysates of erythrocytes and homogenates of hepatic tissue. The severity of the cholestasis and hepatic injury were determined by the changes in the plasma enzyme activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AP), g-glutamyl-transpeptidase (GGT), and levels of albumin, total bilirubin (TB) and direct bilirubin (DB). Either melatonin or S-AMe were administered daily 3 days before LBD, and for 10 days after biliary obstruction. LDB caused highly significant increases in plasma enzyme activities and in bilirubin and lipid peroxides levels in erythrocytes and hepatic tissue. At the same time, this procedure produced a notable decrease in the GSH pools in these biological media. Both melatonin and S-AMe administration were effective as antioxidants and hepatoprotective substances, although the protective effects of melatonin were superior; it prevented the GSH decrease and reduced significantly the increases in enzyme activities and lipid peroxidation products produced by biliary ligature. S-AMe did not modify the increased GGT activity nor did it decrease greatly the TB levels (43% melatonin vs. 14% S-AMe). However, S-AMe was effective in preventing the loss of GSH in erythrocytes and hepatic tissue, as was melatonin. The obtained data permit the following conclusions. First, the LDB models cause marked hepatic oxidative stress. Second, the participation of free radicals of oxygen in the pathogenecity and severity of cholestasis produced by the acute obstruction of the extra-hepatic biliary duct is likely. Third, the results confirm the function of S-AMe as an antioxidant and hepatoprotector. Finally, melatonin is far more potent and provides superior protection as compared to S-AMe. Considering the decrease in oxidative stress and the intensity of cholestasis, these findings have interesting clinical implications for melatonin as a possible therapeutic agent in biliary cholestasis and parenchymatous liver injury.     

From the Cover: Spray-combustion synthesis: Efficient solution route to high-performance oxide transistors

Metal-oxide (MO) semiconductors have emerged as enabling materials for next generation thin-film electronics owing to their high carrier mobilities, even in the amorphous state, large-area uniformity, low cost, and optical transparency, which are applicable to flat-panel displays, flexible circuitry, and photovoltaic cells. Impressive progress in solution-processed MO electronics has been achieved using methodologies such as sol gel, deep-UV irradiation, preformed nanostructures, and combustion synthesis. Nevertheless, because of incomplete lattice condensation and film densification, high-quality solution-processed MO films having technologically relevant thicknesses achievable in a single step have yet to be shown. Here, we report a low-temperature, thickness-controlled coating process to create high-performance, solution-processed MO electronics: spray-combustion synthesis (SCS). We also report for the first time, to our knowledge, indium-gallium-zinc-oxide (IGZO) transistors having densification, nanoporosity, electron mobility, trap densities, bias stability, and film transport approaching those of sputtered films and compatible with conventional fabrication (FAB) operations.Metal-oxide (MO) semiconductors, especially in amorphous phases, represent an appealing materials family for next generation electronics owing to their high carrier mobilities, good environmental/thermal stability, mechanical flexibility, and excellent optical transparency (1–3). MO films complement organic semiconductors (4, 5), carbon/oxide nanomaterials (6), and flexible silicon (7, 8) for enabling new technologies, such as flexible displays and printed sensors. For fabricating high-performance electronics with acceptable fidelity, conventional processes require capital-intensive physical/chemical vapor deposition techniques. Capitalizing on the solubility of MO precursors in common solvents, solution methods have been used to fabricate semiconducting MO layers for thin-film transistors (TFTs). However, the fabrication process and field-effect mobilities of these TFTs are not competitive with the corresponding vapor-deposited (e.g., sputtered) devices (9), and developing routes to solution-derived MO TFTs with technologically relevant thicknesses and performance comparable to state of the art vapor-deposited devices is a critical milestone for MO electronics evolution.Sol-gel techniques are used extensively for MO film growth, including films for high-performance TFTs (10–13). However, the required sol-gel condensation, densification, and impurity removal steps typically require >400–500 °C processing temperatures, which are incompatible with inexpensive glasses and typical flexible plastic substrates (14). Progress toward significantly reducing the processing temperatures of sol gel-derived MO films has afforded excellent TFT mobilities; however, achieving both reproducible high-performance and stable device operation remains an unsolved issue for Ga-containing materials (15). Sol-gel on-a-chip for indium-zinc-oxide (3) and deep-UV irradiation of spin-coated MO precursor films (1) represent significant advances; however, challenges remain. Recently, this laboratory reported a low-temperature solution method, spin-coating combustion synthesis (spin-CS), for fabricating MO TFTs (SI Appendix, Fig. S1) (2, 16). By incorporating an oxidizer and a fuel in the precursor solution, localized, highly exothermic chemical transformations occur within the spin-coated films, effecting rapid condensation and M-O-M lattice formation at temperatures as low as 200–300 °C, which was assessed by thermal and X-ray diffraction (XRD) analysis, and yielding high-performance TFTs. Additional work has subsequently broadened the spin-CS fuel/oxidizer options and accessible MO compositions (17).Note, however, that independent of the particular solution processing method, significant quantities of gaseous H₂O, N₂, NO_x, CO₂, etc. are evolved, compromising film continuity and densification in single-step, thick-film growth processes (17–21). These issues also apply to combustion synthesis, especially because the exotherm is of short duration. Therefore, films must be sufficiently thin (typically <10–20 nm for conventional sol gel and <5–10 nm for combustion) to yield high-quality films (2, 3, 15). For MO TFT implementation in, for example, active-matrix display backplanes, semiconductor thicknesses must be 50–100 nm to avoid back-channel effects, delayed turn-on, and bias stress shifting (22, 23). Thus, for current generation MO TFT structures, suitable film thicknesses from conventional solution processes require inefficient multiple deposition and anneal sequences, which are time-consuming, and invariably create bulk trap states at the semiconductor interfaces.In contrast to spin coating, spray processes are readily adapted to continuous large-area, high-throughput coating as in roll-to-roll processing. Simple spray coating has been used to fabricate organic solar cells (24), organic TFTs (25), and MO electronics (26) using heated substrates. In pioneering work, spray-coated sol-gel ZnO TFTs achieved mobilities of ∼0.1 cm² V⁻¹ s⁻¹ for 200 °C growth and ∼25 cm² V⁻¹ s⁻¹ for 500 °C growth (26). These results raise the intriguing question of whether combustion processing can be combined with spray coating to realize, at low temperatures, dense high-mobility MO films having significant, precisely controlled thicknesses in a single step and specifically, growing the most technologically relevant oxide film materials: semiconducting indium-gallium-tin oxide (IGZO) and conducting indium-tin-oxide (ITO).Here, we report a low-temperature, nanometer-thickness, controlled solution route to high-performance MO electronics through spray-combustion synthesis (SCS). Reduced gaseous byproduct trapping yields dense, high-quality, macroscopically continuous films of both crystalline and amorphous MOs. Single-layer (50-nm-thick) IGZO TFTs with carrier mobilities 10²–10⁴× greater (7–20 cm²/Vs) than those achieved with sol gel and conventional combustion synthesis are demonstrated and rival those of magnetron-sputtered IGZO TFTs. Film characterization includes the first positron annihilation spectroscopy (PAS) measurements on oxide thin films to our knowledge, X-ray photoelectron spectroscopy (XPS), X-ray reflectivity (XRR), and capacitance-voltage (C-V) data, supporting the broad applicability of SCS.     

Prognostic influence of the third Gleason grade in prostatectomy specimens

BackgroundGleason grading of prostatic specimens remains as one of the most powerful factors predicting prognosis in patients with prostate cancer. This grading system was created by Donald Gleason about 49 years ago and it takes into account the 2 most prevalent grades in the tumor sample, but it does not consider the presence of a third high grade pattern when it represents less than 5% of the whole radical prostatectomy specimen.ObjectiveThe objective of the present study is to determine whether the existence of a third pattern of growth in the radical prostatectomy samples correlates with a shorter recurrence free survival.Material and methodsWe have reviewed 85 consecutive specimens of radical prostatectomy from patients with clinical localized disease. Those who received previous hormonal or radiation therapy were excluded. We have determined the Gleason grade and also the presence of a third higher grade pattern, surgical margins status, capsular, vascular, and lymphatic invasion. We have analyzed whether the existence of this high grade third pattern areas influences prognosis. Recurrence was defined with PSA levels (biochemical recurrence).ResultsWe have shown that the presence of a Gleason's grade 5 pattern of growth worsens prognosis in patients with tumors grade 7 (both 3 + 4 and 4 + 3), with a shorter time to recurrence. The latter group of patients behaves more like patients with Gleason 8 tumors. This worse prognosis should be taken into account for patient surveillance and future adjuvant therapies. We feel this information is relevant and should be reported in the pathology reports.     

Association of Carcinoid Tumor and Sarcoidosis

The association of systemic sarcoidosis with malignant neoplasms has been reported by several publications although there is controversy as to whether sarcoidosis predisposes patients to certain types of tumors or whether it is the tumors that cause a sarcoid reaction. The relationship between endobronchial carcinoid tumor and sarcoidosis is uncommon. We report the case of a 43-year-old male who was hospitalized due to hemoptysis. Thoracic CT revealed a pulmonary mass in the right upper lobe (RUL) as well as hypermetabolic lymphadenopathies seen with PET-CT. The endobronchial biopsies were compatible with carcinoid tumor. The patient underwent lobectomy of the RUL with mediastinal lymphadenectomy. Histology demonstrated type I endobronchial carcinoid tumor and sarcoid granulomas, both in the RUL surgical piece as well as in the mediastinal lymph nodes.