Keeping an eye on myocilin: a complex molecule associated with primary open-angle glaucoma susceptibility

MYOC encodes a secretary glycoprotein of 504 amino acids named myocilin. MYOC is the first gene to be linked to juvenile open-angle glaucoma (JOAG) and some forms of adult-onset primary open-angle glaucoma (POAG). The gene was identified as an up-regulated molecule in cultured trabecular meshwork (TM) cells after treatment with dexamethasone and was originally referred to as trabecular meshwork-inducible glucocorticoid response (TIGR). Elevated intraocular pressure (IOP), due to decreased aqueous outflow, is the strongest known risk factor for POAG. Increasing evidence showed that the modulation of the wild-type (wt) myocilin protein expression is not causative of glaucoma while some misfolded and self-assembly aggregates of mutated myocilin may be associated with POAG in related or unrelated populations. The etiology of the disease remains unclear. Consequently, a better understanding of the molecular mechanisms underlying POAG is required to obtain early diagnosis, avoid potential disease progression, and develop new therapeutic strategies. In the present study, we review and discuss the most relevant studies regarding structural characterizations, expressions, molecular interactions, putative functions of MYOC gene and/or its corresponding protein in POAG etiology.     

Antioxidant capacity and phenolic content of Caesalpinia pyramidalis Tul. and Sapium glandulosum (L.) Morong from Northeastern Brazil

The aims of this study were to quantify the phenolic content and evaluate the antioxidant potential of extracts from the bark and leaves of C. pyramidalis and S. glandulosum. The total phenolic content (TPC) and total tannin content (TTC) were determined using the Folin-Ciocalteu method, and the total flavonoids content (TFC) was measured via complexation with aluminum chloride. The antioxidant activity was evaluated with DPPH (2.2-diphenyl-1-picrylhydrazyl) and FIC (ferrous ion chelating) assays. The TPC ranged between 135.55 ± 9.85 and 459.79 ± 11.65 tannic acid equivalents (TAE) in mg/g material (mg TAE/g). The leaves of both species contained high levels of tannins and flavonoids. The crude ethanol extracts (CEE) from the bark of C. pyramidalis showed high antioxidant activity when compared to ascorbic acid and rutin, whereas the CEE from the leaves was more efficient in chelating ferrous ions. C. pyramidalis had very high phenolic content and anti-radical activity, which indicates a need for further studies aimed at the purification and identification of compounds responsible for the antioxidant activity.     

Determination of lumiracoxib by a validated stability‐indicating MEKC method and identification of its degradation products by LC‐ESI‐MS studies

A stability‐indicating MEKC method was developed and validated for the analysis of lumiracoxib (LMC) in pharmaceutical formulations using nimesulide as the internal standard (IS). Optimal conditions for the separation of LMC and degradation products were investigated. The method employed 50 mM borate buffer and 50 mM anionic detergent SDS solution at pH 9.0. MEKC method was performed on a fused‐silica capillary (50 μm id; effective length, 40 cm) maintained at 30°C. The applied voltage was 20 kV and photodiode array (PDA) detector was set at 208 nm. The method was validated in accordance with the International Conference on Harmonisation requirements. The stability‐indicating capability of the method was established by enforced degradation studies combined with peak purity assessment using PDA detection. The degradation products formed under stressed conditions were investigated by LC‐ESI‐MS and the two degraded products were identified. MEKC method was linear over the concentration range of 5–150 μg/mL (r²=0.9999) of LMC. The method was precise, accurate, with LOD and LOQ of 1.34 and 4.48 μg/mL, respectively. The robustness was proved by a fractional factorial design evaluation. The proposed MEKC method was successfully applied for the quantitative analysis of LMC in tablets to support the quality control.     

Asymmetric heterobimetallic mixed-valence complex trans-[(SO3)Co(cyclam)(NCS)Ru(NH3)4(NCS)](BF4): Synthesis and characterization

[(SO₃)Co(cyclam)(NCS)] and [(SO₃)Co(cyclam)-NCS-Ru(NH₃)₄(NCS)](BF₄) complexes were synthesized and characterized by means of X-ray diffraction, electrochemistry, elemental analysis, and spectroscopic techniques. Crystallographic and FTIR data indicated NCS⁻ ligand is coordinated to Co through the nitrogen atom in the monomer species. Electrochemistry and FTIR data of the material isolated after reductive electrolysis of [(SO₃)Co(cyclam)(NCS)] hint that NCS⁻ and SO₃²⁻ are released thus forming [Co(cyclam)(L)₂]²⁺, where L is solvent molecules. The formation of the heterobimetallic mixed-valence complex induced a thermodynamic stabilization of Co and Ru metal atoms in the oxidized and reduced states, respectively. According to the Robin and Day classification, a Class II system with a comproportionation constant of 5.78 × 10⁶ is suggested for the mixed-valence complex based on the electrochemical and UV-Vis-NIR results.     

Performance of Ex Situ Bismuth Film Rotating Disk Electrode in Trace Metal Analysis by Stripping Chronopotentiometry: Definition of the Depletion Regime and Optimization of Experimental Parameters

The potentiality of the ex situ deposited bismuth film electrode, allied to the rotation of a glassy carbon disk electrode (BiFE‐RDE), was exploited in trace metal analyses of lead(II) and cadmium(II) by stripping chronopotentiometry (SCP). A single BiFE (6.2 nm film thickness) can be used for a 1‐day term with no significant variation in the analytical signal. The limit of detection (3σ) for a deposition time of 40 s and an oxidation current of 15×10^?9 A was 1.5×10^?8 M for Pb(II) and 3.0×10^?8 M for Cd(II). BiFE‐RDE was successfully applied to the direct SCP determination of lead(II) in a fresh water certified material.     

Metalloprobes for functional monitoring of tumour multidrug resistance by nuclear imaging

Cancer chemotherapy has been used since the early 1950s and still remains one the major therapeutic options for many malignant tumours. A major obstacle to successful cancer chemotherapy is drug resistance. Frequently resistance is intrinsic to the cancer, but as therapy becomes more effective, acquired resistance has also become more frequent. One form of resistance, named multidrug resistance (MDR), is responsible for the failure of tumours to respond to a wide spectrum of chemotherapeutic agents. The in vivo monitoring of MDR could assist in the selection of patients for therapy and can avoid ineffective and potentially toxic treatments. Therefore, methods for functionally interrogating MDR transport activity have been sought, namely single photon emission computed tomography (SPECT) and positron emission tomography (PET). Cationic radiotracers originally developed as SPECT myocardial imaging agents, such as [(99m)Tc(MIBI)(6)](+) and [(99m)Tc(tetrofosmin)(2)O(2)](+), are used for both early cancer detection and non-invasive monitoring of the tumour MDR transport function. With the ultimate goal of obtaining better performing radioprobes for MDR imaging, other metal-based complexes and/or small molecules have also been synthesized and biologically evaluated. In this perspective we will report on the chemical efforts made to find metalloprobes for in vivo monitoring of MDR by nuclear imaging techniques. The current knowledge on the biological mechanisms and proteins involved in tumour MDR will be also briefly presented, as its understanding is invaluable for the rational design and biological evaluation of new radioprobes.     

The relation between structural features and electrochemical activity of MnO2 nanoparticles synthesized from a polyol-made Mn3O4 precursor

A simple hybrid synthesis processing method was developed to synthesize γ-MnO₂ nanocrystalline particles. The polyol method was modified by the addition of nitric acid in order to allow the synthesizing of single-phase Mn₃O₄ in a large scale. In the sequence, the acid digestion technique was used to transform Mn₃O₄ into γ-MnO₂. Structural and morphological characterization was carried out by X-ray diffractometry, Infrared and Raman spectroscopy, thermogravimetric analysis, nitrogen adsorption isotherm, scanning electron microscopy, and transmission electron microscopy. The electrochemical properties were investigated by cyclic voltammetry and galvanostatic charge–discharge measurements. The synthesized material exhibits a specific capacitance of 125.1 F?g^?1 at a mass loading of 0.98 mg?cm^?2. The relation between structural features and electrochemical activity is discussed by comparing the synthesized material with commercial electrolytic manganese dioxide.     

Determination of the Natural Dissolved Concentration of Zirconium in Seawater by Adsorptive Stripping Voltammetry

A voltammetric method was developed for zirconium determination as Zr(IV)‐cupferron‐oxalate‐diphenylguanidine complex based on adsorptive accumulation at the HMDE (E_peak=?0.95 V). The supporting electrolyte was a mixture of acetate/acetic acid (pH 4.6) and ammonium acetate (pH 5.7) solutions. E_ads=?0.6 V (vs. Ag/AgCl), t_ads=400 s, 10 mV s^?1 scan rate, and DP mode were the main parameters. The linear range was 0.033 to 3.3×10^?9 mol L^?1, and the LOD and LOQ (t_ads=400 s) were 0.77 and 1.6×10^?11 mol L^?1, respectively. The method was adequate for seawater samples, although not sufficiently sensitive for surface waters.     

Synthesis and crystal structure of some new cadmium (II) macrocyclic Schiff-base complexes containing piperazine moiety

The metal templated Cd(II) cyclocondensation of 2,6-diacetylpiridine or 2,6-pyridinedicarbaldehyde and two different amines containing piperazine moieties have been investigated. The resulting ligands, L¹ and L² are 16- and L³ and L⁴ 17-membered pentaaza macrocycles. The complexes have been characterized by a variety of methods including IR, ¹H, ¹³C NMR, DEPT, COSY(H,H), HMQC(H,C), FAB spectrometry and conductivimetry measurements. The crystal structures of [CdL²Cl](CH₃OH)ClO₄ (2) and [CdL⁴(NO₃)(H₂O)]ClO₄ (4) have been also determined, and it was shown that the geometry of the Cd(II) ion in the complexes is slightly distorted pentagonal pyramidal and pentagonal bipyramidal, respectively. The gas-phase structures of ligands, L² and L⁴ and their Cd(II) complexes have also theoretically studied.     

Voltammetric determination of Se(IV) and Se(VI) in saline samples—Studies with seawater, hydrothermal and hemodialysis fluids

Determination of Se(IV) and Se(VI) in high saline media was investigated by cathodic stripping voltammetry (CSV). The voltammetric method was applied to assay selenium in seawater, hydrothermal and hemodialysis fluids. The influence of ionic strength on selenium determination is discussed. The CSV method was based on the co-electrodeposition of Se(IV) with Cu(II) ions and Se(VI) determined by difference after sample UV-irradiation for photolytic selenium reduction. UV-irradiation was also used as sample pre-treatment for organic matter decomposition. Detection limit of 0.030 μg L⁻¹ (240 s deposition time) and relative standard deviation (RSD) of 6.19% (n = 5) for 5.0 μg L⁻¹ of Se(IV) were calculated. Linear calibration range for selenium was observed from 1.0 to 100.0 μg L⁻¹. Concerning the pre-treatment step, best results were obtained by using 60 min UV-irradiation interval in H₂O₂/HCl medium. Se(VI) was reduced to the Se(IV) electroactive species with recoveries between 91.7% and 112.9%. Interferents were also investigated.