Multivariate QSAR, similarity search and ADMET studies based in a set of methylamine derivatives described as dopamine transporter inhibitors.

The dopamine transporter (DAT), responsible for the regulation of dopaminergic neurotransmission, is implicated in the etiology of several neuropsychiatric disorders which, in turn, have contributed to high rates of disability and numerous deaths in recent years, significantly impacting the global health system. Although the research for new drugs for the treatment of neuropsychiatric disorders has evolved in recent years, the availability of DAT-selective drugs that do not generate the same psychostimulant effects observed in drugs of abuse remains scarce. Therefore, we performed a QSAR study based on a dataset of 36 methylamine derivatives described as DAT inhibitors. The model was obtained based only in descriptors derived from 2D structures, and it was validated and generated satisfactory results considering the metrics used for internal and external validation. Subsequently, a virtual screening step also based on 2D similarity was performed, where it was possible to identify a total of 1157 compounds. After a series of reductions of the set using toxicity filters, applicability domain evaluation, and pharmacokinetic properties in silico assessment, seven hit compounds were selected as the most promising to be used, in future studies, as new scaffolds for the development of new DAT inhibitors.

Quality and Disposal of Dredged Sediments from Tidal Deltas in Subtropical Bays in Southern Brazil.

In order to measure the contamination of dredged and beach sediments and the applicability of sediment quality guidelines in a wet subtropical region of southern Brazil, the areas surrounding both the Paranaguá and Babitonga estuaries were studied, including their harbour zones and adjacent beaches. Investigation of the sampled sediments comprised optical and electron microscopy, energy-dispersive X-ray spectroscopy, inductively coupled plasma mass spectrometry, and physicochemical and toxicological analyses. Additionally, data provided by the harbours administrations on dredged volumes, sedimentology, and coastal dynamics were compared. It was determined that the studied sediments, especially the ones from both tidal deltas, have similar characteristics, including physical and chemical parameters. It was also confirmed that tidal deltas are depositional areas with low potential to accumulate pollutants. Therefore, the current disposal of this scarce sandy material during dredging might not be beneficial, considering the significant sand removal amount from the coastal depositional system.

Baseline-Corrected Second-Order Derivative Electroanalysis Combined With Ultrasound-Assisted Liquid-Liquid Microextraction: Simultaneous Quantification of Fluoroquinolones at Low Levels.

A baseline-corrected second-order derivative procedure and a miniaturized sample preparation based on low-density solvent and ultrasound-assisted liquid-liquid microextraction (LDS-UA-LLME) was combined to provide the simultaneous electroanalysis of three fluoroquinolones (FQ) as emerging contaminants (ECs). The enhanced mathematical processing provided the best separation with an accurate measurement of the overlapping peaks during the simultaneous electro-oxidation of target FQs that were directly dropped on the surface of carbon nanofiber-modified screen-printed electrodes. The adapted LDS-UA-LLME protocol was the key step involved in the sample preparation, which preconcentrate target analytes from diluted tap water samples with an enrichment factor of around 80×, allowing their quantification at trace levels. This combined feature demonstrated the unique application of an electroanalytical technique for the simultaneous electroanalysis of three FQs in spiked tap water samples, with recovery values remarkably close to 100%.

Chronoamperometric flow-cell designed to be unaffected by air bubbles.

In this paper, we present a new design for a chronoamperometric flow cell in which air bubbles do not interfere with the control of potential between the working and reference electrodes. The flow-through dual-detection cell consists of two independent parts: an upper compartment containing a quiescent supporting electrolyte solution and a channel that operates under hydrodynamically controlled conditions. In this system, the working and counter electrodes can be placed directly in contact with both compartments, whereas the reference electrode can be assembled to be either isolated or in contact with the flowing stream channel. The design ensures that the potential applied to the working electrode (controlled in the upper compartment) is similar to the potential applied in the flowing channel. The performance of the proposed flow cell in generating accurate results, even in the presence of air bubbles, was evaluated through successive air-analyte-air injections. In both series where the analyte was introduced, suitable reproducibility was achieved. The robustness of the design was definitively proven by performing a series of measurements in analytical applications for the determination of hydrogen peroxide in antiseptic samples, yielding very satisfactory results.

Sample preparation combined with electroanalysis to improve simultaneous determination of antibiotics in animal derived food samples.

A procedure based on liquid-liquid extraction (LLE) and phase separation using magnetically stirred salt-induced high-temperature liquid-liquid extraction (PS-MSSI-HT-LLE) was developed to extract and pre-concentrate ciprofloxacin (CIPRO) and enrofloxacin (ENRO) from animal food samples before electroanalysis. Firstly, simple LLE was used to extract the fluoroquinolones (FQs) from animal food samples, in which dilution was performed to reduce interference effects to below a tolerable threshold. Then, adapted PS-MSSI-HT-LLE protocols allowed re-extraction and further pre-concentration of target analytes in the diluted acid samples for simultaneous electrochemical quantification at low concentration levels. To improve the peak separation, in simultaneous detection, a baseline-corrected second-order derivative approach was processed. These approaches allowed quantification of target FQs from animal food samples spiked at levels of 0.80 to 2.00 µmol L-1 in chicken meat, with recovery values always higher than 80.5%, as well as in milk samples spiked at 4.00 µmol L-1, with recovery values close to 70.0%.

A new method to evaluate glenoid erosion in instable shoulder.

BACKGROUND: We aimed to establish values and parameters using multislice reconstruction in axial computerized tomography (CT) in order to quantify the erosion of the glenoid cavity in cases of shoulder instability. METHODS: We studied two groups using CT. Group I had normal subjects and Group II had patients with shoulder instability. We measured values of the vertical segment, the superior horizontal, medial and inferior segments, and also calculated the ratio of the horizontal superior and inferior segments of the glenoid cavity in both normal subjects and those with shoulder instability. These variables were recorded during arthroscopy for cases with shoulder instability. RESULTS: The mean values were 40.87 mm, 17.86 mm, 26.50 mm, 22.86 mm and 0.79 for vertical segment, the superior horizontal, medial and inferior segments, and the ratio between horizontal superior and inferior segments of the glenoid cavity respectively, in normal subjects. For subjects with unstable shoulders the mean values were 37.33 mm, 20.83 mm, 23.07 mm and 0.91 respectively. Arthroscopic measurements yielded an inferior segment value of 24.48 mm with a loss of 2.39 mm (17.57%). The ratio between the superior and inferior segments of the glenoid cavity was 0.79. This value can be used as a normative value for evaluating degree of erosion of the anterior border of the glenoid cavity. However, values found using CT should not be used on a comparative basis with values found during arthroscopy. CONCLUSIONS: Computerized tomographic measurements of the glenoid cavity yielded reliable values consistent with those in the literature.