Comportamento hidráulico da rede de drenagem pluvial do bairro santa mônica com o uso do software swmm

As a result of urban development carried out in a disordely way, it is evident that some sectors of municipal infrastructure become obsolete over time, which is the case of rainwater drainage. In Uberlandia-MG, several neighborhoods in the city suffer from flooding during the rainy season.Due to its social importance to the city, the Santa Mônica neighborhood, where the Federal University of Uberlândia is located, was chosen as the study area of this work, which aims to obtain results regarding the capacity of the existing rainwater drainage network, as well as to map likely points flooding, that is, points of necessary reinforcement in the rainwater network.Through the registration of existing galleries, made available by the Municipal Department of Water and Sewage (DMAE), and using the Storm Water Management Model (SWMM) software, it was possible to analyze the real condition of the rainwater drainage system in the neighborhood.The results obtained by this work corroborate the initial suspicion observed in the field during the rainy seasons, that the current existing network does not satisfactorily support the necessary water volume, which leads to several points of overload and flooding spread throughout the neighborhood. at risk the traffic of people and vehicles.USIMINAS - Usinas Siderúrgicas de Minas Gerais S/ATrabalho de Conclusão de Curso (Graduação)Como consequência do desenvolvimento urbano realizado de forma desordenada, é evidente que alguns setores de infraestrutura municipal se tornam obsoletos com o passar do tempo, que é o caso da drenagem pluvial. Em Uberlândia-MG, diversos bairros da cidade apresentam alagamentos e enchentes no período chuvoso. Pela sua importância social perante a cidade, o bairro Santa Mônica, onde fica localizada a Universidade Federal de Uberlândia, foi escolhido como área de estudo deste trabalho, que visa obter resultados quanto à capacidade da rede de drenagem pluvial existente, assim como mapear prováveis pontos de alagamentos, ou seja, pontos de necessários reforços na rede pluvial. Através do cadastro de galerias existentes, disponibilizado pelo Departamento Municipal de Água e Esgoto (DMAE), e com a utilização do software Storm Water Management Model (SWMM), foi possível analisar a real condição do sistema de drenagem pluvial do bairro. Os resultados obtidos por esse trabalho corroboram com a suspeita inicial observada em campo nos períodos chuvosos, de que a rede atual existente não suporta de maneira satisfatória o volume de água necessário, o que leva a diversos pontos de sobrecargas e alagamentos espalhados pelo bairro, colocando em risco o tráfego de pessoas e veículos

Host-Guest interaction between herbicide oxadiargyl and hydroxypropyl-β-cyclodextrin

In the face of a growing human population and increased urbanization, the demand for pesticides will simply rise. Farmers must escalate yields on increasingly fewer farm acres. However, the risks of pesticides, whether real or perceived, may force changes in the way these chemicals are used. Scientists are working toward pest control plans that are environmentally sound, effective, and profitable. In this context the development of new pesticide formulations which may improve application effectiveness, safety, handling, and storage can be pointed out as a solution. As a contribution to the area, the microencapsulation of the herbicide oxadiargyl (OXA) in (2-hydroxypropyl)-β-cyclodextrin (HP-β-CD) was performed. The study was conducted in different aqueous media (ultrapure water and in different pH buffer solutions). In all cases an increment of the oxadiargyl solubility as a function of the HP-β-CD concentration that has been related to the formation of an inclusion complex was verified. UV-Vis and NMR experiments allowed concluding that the stoichiometry of the OXA/HP-β-CD complex formed is 1 : 1. The gathered results can be regarded as an important step for its removal from industrial effluents and/or to increase the stabilizing action, encapsulation, and adsorption in water treatment plants

Exploring the Multi-Target Performance of Mitochondriotropic Antioxidants against the Pivotal Alzheimer’s Disease Pathophysiological Hallmarks

Alzheimer disease (AD) is the most common neurodegenerative disease featuring progressive and degenerative neurological impairments resulting in memory loss and cognitive decline. The specific mechanisms underlying AD are still poorly understood, but it is suggested that a deficiency in the brain neurotransmitter acetylcholine, the deposition of insoluble aggregates of fibrillar β-amyloid 1–42 (Aβ42), and iron and glutamate accumulation play an important role in the disease progress. Despite the existence of approved cholinergic drugs, none of them demonstrated effectiveness in modifying disease progression. Accordingly, the development of new chemical entities acting on more than one target is attracting progressively more attention as they can tackle intricate network targets and modulate their effects. Within this endeavor, a series of mitochondriotropic antioxidants inspired on hydroxycinnamic (HCA’s) scaffold were synthesized, screened toward cholinesterases and evaluated as neuroprotectors in a differentiated human SH-SY5Y cell line. From the series, compounds 7 and 11 with a 10-carbon chain can be viewed as multi-target leads for the treatment of AD, as they act as dual and bifunctional cholinesterase inhibitors and prevent the neuronal damage caused by diverse aggressors related to protein misfolding and aggregation, iron accumulation and excitotoxicityThis work was funded by FEDER funds through the Operational Programme Competitiveness Factors-COMPETE and national funds by FCT-Foundation for Science and Technology under research grants (UID/QUI/00081, NORTE-01-0145-FEDER-000028, PTDC/DTP-FTO/2433/2014, PTDC/BIA-MOL/28607/2017, POCI-01-0145-FEDER-028607). S. Benfeito and C. Fernandes grants are supported by FCT, POPH and QREN. The authors also thank the COST action CA15135 for supportS

The versatility of membrane-water partitioning in pharmacokinetic modelling

info:eu-repo/semantics/publishedVersio

Drug biophysical profiling using lipid-based colloidal nanosystems and human serum albumin as biomimetic interfaces

The development of new drugs is a highly complex and expensive process, so it is crucial that less promising compounds are rejected early in the discovery phase before progressing to more expensive phases. This scenario impels researchers to refine and speed up the drug discovery process and to seek tools to support decisions related to modifications of the drug chemical structure to improve drugs’ properties and thus increase the probability of success in the process of drug discovery. [1], [2] In the drug discovery process it should be considered that in physiological environment there will be reciprocal interactions between drugs and biological interfaces, such as cell membranes or plasma proteins, and from those interactions different pharmacokinetic profiles can be achieved. [3] Thus, it is important to develop in vitro high throughput methods to evaluate the pharmaceutical profile, consisting in measuring properties such as permeability, lipophilicity, plasma protein binding, and biophysical changes of the membranes, which in turn affect other properties, such as the bioavailability of a drug and its pharmacokinetic profile. [4] Herein, the characterization of a newly synthesized drug (MIT-3) will be based on the measurement of fundamental biophysical properties, which allow inferring about its ADMET profile (absorption, distribution, excretion and toxicity at the membrane level). For this purpose, lipid-based colloidal nanosystems of different compositions were prepared as membrane mimetic models and several biophysical techniques were applied: derivative spectroscopy; quenching of steady-state and time-resolved fluorescence; quenching of intrinsic fluorescence of human serum albumin; synchronous fluorescence; dynamic and electrophoretic light scattering, differential scanning calorimetry and small and wide angle x-ray diffraction. The application of these techniques allowed to predict that MIT-3 has an ubiquitous location at the membrane level, presenting good membrane permeability and a good distribution in the therapeutic target. However, it is also predicted bioaccumulation with distribution in non-therapeutic targets and under conditions of prolonged exposure the drug may cause membrane toxicity as concluded by the impairment of membrane biophysical properties. It is also possible to conclude that the biophysical techniques and the biomimetic models used, constitute a toolbox of strategies for the future evaluation of other drugs.This work was supported by the Portuguese Foundation for Science and Technology (FCT) in the framework of the Strategic Funding UID/FIS/04650/2013. We also acknowledge PEstC/QUI/UI0081/2013, NORTE-01-0145-FEDER-000028 and PTDC/DTP-FTO/2433/2014. F. Cagide and S. Benfeito are thankful for the pos-doctoral and doctoral grants (SFRH/BPD/74491/2010 and SFRH/BD/99189/2013 respectively). Marlene Lúcio acknowledges the exploratory project funded by FCT with the reference IF/00498/2012. Eduarda Fernandes acknowledges COMPETE 2020 “Programa Operacional Competitividade e internacionalização”.info:eu-repo/semantics/publishedVersio

Fine-tuning of the hydrophobicity of caffeic acid: studies on the antimicrobial activity against Staphylococcus aureus and Escherichia coli

The increased bacterial multidrug resistance caused by inappropriate use and overuse of antimicrobials is a global concern. To circumvent this issue, a quest for the development of new active agents has been widely recognized. Some phytochemical products, produced by plants as part of their chemical defense strategies, are regarded as new stimulii to develop novel antimicrobials that are not as vulnerable as current drugs to bacterial resistance mechanisms. In this study, the antimicrobial activity and mode of action of caffeic acid (CAF) and a series of CAF alkyl esters was assessed against Escherichia coli and Staphylococcus aureus, with the aim of analyzing the influence of the alkyl ester side chain length on the activity. Minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), changes in physicochemical surface properties and intracellular potassium leakage were used as physiological indices for the antimicrobial mode of action. CAF alkyl esters were found to be effective antimicrobial agents against both bacteria. Their activity was directly dependent on their lipophilicity, which affected bacterial susceptibility, the physicochemical properties of the bacteria and the integrity of the membranes. E. coli was less susceptible than S. aureus to the action of the compounds. Longer alkyl side chains were more effective against the Gram-positive bacterium, while medium length alkyl side chain compounds were more effective against the Gram-negative bacterium. Caffeic acid derivatives are proposed to act as cell permeabilizers, inducing membrane alterations, causing rupture with potassium leakage, particularly on the Gram positive bacterium, and consequent cell death

Fine-Tuning the Biological Profile of Multitarget Mitochondriotropic Antioxidants for Neurodegenerative Diseases

Neurotransmitter depletion and mitochondrial dysfunction are among the multiple pathological events that lead to neurodegeneration. Following our previous studies related with the development of multitarget mitochondriotropic antioxidants, this study aims to evaluate whether the π-system extension on the chemical scaffolds of AntiOXCIN2 and AntiOXCIN3 affects their bioactivity and safety profiles. After the synthesis of four triphenylphosphonium (TPP+) conjugates (compounds 2-5), we evaluated their antioxidant properties and their effect on neurotransmitter-metabolizing enzymes. All compounds were potent equine butyrylcholinesterase (eqBChE) and moderate electric eel acetylcholinesterase (eeAChE) inhibitors, with catechols 4 and 5 presenting lower IC50 values than AntiOXCIN2 and AntiOXCIN3, respectively. However, differences in the inhibition potency and selectivity of compounds 2-5 towards non-human and human cholinesterases (ChEs) were observed. Co-crystallization studies with compounds 2-5 in complex with human ChEs (hChEs) showed that these compounds exhibit different binging modes to hAChE and hBChE. Unlike AntiOXCINs, compounds 2-5 displayed moderate human monoamine oxidase (hMAO) inhibitory activity. Moreover, compounds 4 and 5 presented higher ORAC-FL indexes and lower oxidation potential values than the corresponding AntiOXCINs. Catechols 4 and 5 exhibited broader safety windows in differentiated neuroblastoma cells than benzodioxole derivatives 2 and 3. Compound 4 is highlighted as a safe mitochondria-targeted antioxidant with dual ChE/MAO inhibitory activity. Overall, this work is a contribution for the development of dual therapeutic agents addressing both mitochondrial oxidative stress and neurotransmitter depletion

Cytotoxicity and Mitochondrial Effects of Phenolic and Quinone-Based Mitochondria-Targeted and Untargeted Antioxidants on Human Neuronal and Hepatic Cell Lines: A Comparative Analysis

Mitochondriotropic antioxidants (MC3, MC6.2, MC4 and MC7.2) based on dietary antioxidants and analogs (caffeic, hydrocaffeic, trihydroxyphenylpropanoic and trihydroxycinnamic acids) were developed. In this study, we evaluate and compare the cytotoxicity profile of novel mitochondria-targeted molecules (generally known as MitoCINs) on human HepG2 and differentiated SH-SY5Y cells with the quinone-based mitochondria-targeted antioxidants MitoQ and SkQ1 and with two non-targeted antioxidants, resveratrol and coenzyme Q10 (CoQ10). We further evaluate their effects on mitochondrial membrane potential, cellular oxygen consumption and extracellular acidification rates. Overall, MitoCINs derivatives reduced cell viability at concentrations about six times higher than those observed with MitoQ and SkQ1. A toxicity ranking for both cell lines was produced: MC4 < MC7.2 < MC3 < MC6.2. These results suggest that C-6 carbon linker and the presence of a pyrogallol group result in lower cytotoxicity. MC3 and MC6.2 affected the mitochondrial function more significantly relative to MitoQ, SkQ1, resveratrol and CoQ10, while MC4 and MC7.2 displayed around 100-1000 times less cytotoxicity than SkQ1 and MitoQ. Based on the mitochondrial and cytotoxicity cellular data, MC4 and MC7.2 are proposed as leads that can be optimized to develop safe drug candidates with therapeutic application in mitochondrial oxidative stress-related diseases