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1.
Artigo em Inglês | MEDLINE | ID: mdl-38652314

RESUMO

PURPOSE: To study the clinical, radiological, and functional outcomes after of radioscapholunate (RSL) fusion for intra-articular malunion of the distal radius. METHODS: This retrospective study included 26 patients (17 males and 9 females) with intra-articular malunion of distal radius fractures who underwent RSL arthrodesis using locked miniplates (without distal scaphoid excision) between 2012 and 2020. Their mean age was 43 years (range, 32-56). Patients were assessed radiographically for union and clinically for range of motion, grip strength, and pain (assessed by Visual Analogue Scale (VAS) for pain). Functional evaluation was performed by using the Mayo modified wrist score (MMWS) and the Disabilities for the Arm, Shoulder, and Hand (DASH) questionnaire. RESULTS: All patients showed complete healing at the fusion site after a mean of 8.7 weeks (range, 8-12). The mean follow-up period was 72 months (range, 60-84). The pinch strength improved from a mean of 6.2 kg (range, 3-12) to a mean of 9.8 kg (range, 5-18) which represents 80% of the contralateral side. The mean pinch strength was 7 kg (range, 5-18) which presents 80% of the other side. VAS for pain showed a mean improvement of 72.6%. The DASH score improved to a mean of 19.2 (range, 14-24). The MMWS improved to a mean of 68 (range, 45-86). At the final follow-up period, no degenerative changes were detected in the midcarpal joint. CONCLUSION: RSL arthrodesis (using locked miniplates without distal scaphoid excision) is a reliable surgical procedure to manage cases of radiocarpal OA after intra-articular malunion of distal radius fractures with good clinical and radiological outcomes. LEVEL OF EVIDENCE: Level IV- therapeutic.

2.
Chem Rec ; 24(4): e202300234, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38530060

RESUMO

Silica-derived nanostructured catalysts (SDNCs) are a class of materials synthesized using nanocasting and templating techniques, which involve the sacrificial removal of a silica template to generate highly porous nanostructured materials. The surface of these nanostructures is functionalized with a variety of electrocatalytically active metal and non-metal atoms. SDNCs have attracted considerable attention due to their unique physicochemical properties, tunable electronic configuration, and microstructure. These properties make them highly efficient catalysts and promising electrode materials for next generation electrocatalysis, energy conversion, and energy storage technologies. The continued development of SDNCs is likely to lead to new and improved electrocatalysts and electrode materials. This review article provides a comprehensive overview of the recent advances in the development of SDNCs for electrocatalysis and energy storage applications. It analyzes 337,061 research articles published in the Web of Science (WoS) database up to December 2022 using the keywords "silica", "electrocatalysts", "ORR", "OER", "HER", "HOR", "CO2RR", "batteries", and "supercapacitors". The review discusses the application of SDNCs for oxygen reduction reaction (ORR), oxygen evolution reaction (OER), hydrogen evolution reaction (HER), carbon dioxide reduction reaction (CO2RR), supercapacitors, lithium-ion batteries, and thermal energy storage applications. It concludes by discussing the advantages and limitations of SDNCs for energy applications.

3.
Nat Commun ; 14(1): 7605, 2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-37989737

RESUMO

The electrochemical reduction of carbon dioxide to formic acid is a promising pathway to improve CO2 utilization and has potential applications as a hydrogen storage medium. In this work, a zero-gap membrane electrode assembly architecture is developed for the direct electrochemical synthesis of formic acid from carbon dioxide. The key technological advancement is a perforated cation exchange membrane, which, when utilized in a forward bias bipolar membrane configuration, allows formic acid generated at the membrane interface to exit through the anode flow field at concentrations up to 0.25 M. Having no additional interlayer components between the anode and cathode this concept is positioned to leverage currently available materials and stack designs ubiquitous in fuel cell and H2 electrolysis, enabling a more rapid transition to scale and commercialization. The perforated cation exchange membrane configuration can achieve >75% Faradaic efficiency to formic acid at <2 V and 300 mA/cm2 in a 25 cm2 cell. More critically, a 55-hour stability test at 200 mA/cm2 shows stable Faradaic efficiency and cell voltage. Technoeconomic analysis is utilized to illustrate a path towards achieving cost parity with current formic acid production methods.

4.
Molecules ; 28(4)2023 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-36838757

RESUMO

The design and synthesis of porous carbons for CO2 adsorption have attracted tremendous interest owing to the ever-soaring concerns regarding climate change and global warming. Herein, for the first time, nitrogen-rich porous carbon was prepared with chemical activation (KOH) of commercial melamine formaldehyde resin (MF) in a single step. It has been shown that the porosity parameters of the as-prepared carbons were successfully tuned by controlling the activating temperature and adjusting the amount of KOH. Thus, as-prepared N-rich porous carbon shows a large surface area of 1658 m2/g and a high N content of 16.07 wt%. Benefiting from the unique physical and textural features, the optimal sample depicted a CO2 uptake of up to 4.95 and 3.30 mmol/g at 0 and 25 °C under 1 bar of pressure. More importantly, as-prepared adsorbents show great CO2 selectivity over N2 and outstanding recyclability, which was prominently important for CO2 capture from the flue gases in practical application. An in-depth analysis illustrated that the synergetic effect of textural properties and surface nitrogen decoration mainly determined the CO2 capture performance. However, the textural properties of carbons play a more important role than surface functionalities in deciding CO2 uptake. In view of cost-effective synthesis, outstanding textural activity, and the high adsorption capacity together with good selectivity, this advanced approach becomes valid and convenient in fabricating a unique highly efficient N-rich carbon adsorbent for CO2 uptake and separation from flue gases.


Assuntos
Dióxido de Carbono , Carbono , Carbono/química , Dióxido de Carbono/química , Porosidade , Nitrogênio/química , Polímeros
5.
Curr Med Imaging ; 19(5): 486-493, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35927895

RESUMO

BACKGROUND: Chest High-Resolution Computed Tomography (HRCT) is mandatory for patients with confirmed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and a high Respiratory Rate (RR) because sublobar consolidation is the likely pathological pattern in addition to Ground Glass Opacities (GGOs). OBJECTIVE: The present study determined the correlation between the percentage extent of typical pulmonary lesions on HRCT, as a representation of severity, and the RR and peripheral oxygen saturation level (SpO2), as measured through pulse oximetry, in patients with Reverse Transcriptase Polymerase Chain Reaction (RT-PCR)-confirmed primary (noncomplicated) SARS-CoV-2 pneumonia. METHODS: The present retrospective study was conducted in 332 adult patients who presented with dyspnea and hypoxemia and were admitted to Prince Mohammed bin Abdulaziz Hospital, Riyadh, Saudi Arabia between May 15, 2020 and December 15, 2020. All the patients underwent chest HRCT. Of the total, 198 patients with primary noncomplicated SARS-CoV-2 pneumonia were finally selected based on the typical chest HRCT patterns. The main CT patterns, GGO and sublobar consolidation, were individually quantified as a percentage of the total pulmonary involvement through algebraic summation of the percentage of the 19 pulmonary segments affected. Additionally, the statistical correlation strength between the total percentage pulmonary involvement and the age, initial RR, and percentage SpO2 of the patients was determined. RESULTS: The mean ± Standard Deviation (SD) age of the 198 patients was 48.9 ± 11.4 years. GGO magnitude alone exhibited a significant weak positive correlation with patients' age (r = 0.2; p = 0.04). Sublobar consolidation extent exhibited a relatively stronger positive correlation with RR than GGO magnitude (r = 0.23; p = 0.002). A relatively stronger negative correlation was observed between the GGO extent and SpO2 (r = - 0.38; p = 0.002) than that between sublobar consolidation and SpO2 (r = - 0.2; p = 0.04). An increase in the correlation strength was demonstrated with increased case segregation with GGO extent (r = - 0.34; p = 0.01). CONCLUSION: The correlation between the magnitudes of typical pulmonary lesion patterns, particularly GGO, which exhibited an incremental correlation pattern on chest HRCT, and the SpO2 percentage, may allow the establishment of an artificial intelligence program to differentiate primary SARS-CoV-2 pneumonia from other complications and associated pathology influencing SpO2.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Adulto , Pessoa de Meia-Idade , COVID-19/diagnóstico por imagem , Estudos Retrospectivos , Inteligência Artificial , Saturação de Oxigênio , Tomografia Computadorizada por Raios X/métodos
6.
Molecules ; 27(7)2022 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-35408650

RESUMO

Some new pyrimidine derivatives comprising arylsulfonylhydrazino, ethoxycarbonylhydrazino, thiocarbamoylhydrazino and substituted hydrazone and thiosemicarbazide functionalities were prepared from Biginelli-derived pyrimidine precursors. Heterocyclic ring systems such as pyrazole, pyrazolidinedione, thiazoline and thiazolidinone ring systems were also incorporated into the designed pyrimidine core. Furthermore, fused triazolopyrimidine and pyrimidotriazine ring systems were prepared. The synthesized compounds were evaluated for their calcium channel blocking activity as potential hypotensive agents. Compounds 2, 3a, 3b, 4, 11 and 13 showed the highest ex vivo calcium channel blocking activities compared with the reference drug nifedipine. Compounds 2 and 11 were selected for further biological evaluation. They revealed good hypotensive activities following intravenous administration in dogs. Furthermore, 2 and 11 displayed drug-like in silico ADME parameters. A ligand-based pharmacophore model was developed to provide adequate information about the binding mode of the newly synthesized active compounds 2, 3a, 3b, 4, 11 and 13. This may also serve as a reliable basis for designing new active pyrimidine-based calcium channel blockers.


Assuntos
Bloqueadores dos Canais de Cálcio , Pirimidinas , Animais , Bloqueadores dos Canais de Cálcio/química , Canais de Cálcio , Cães , Estrutura Molecular , Pirimidinas/química , Relação Estrutura-Atividade
7.
Sci Rep ; 11(1): 20476, 2021 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-34650073

RESUMO

The increased frequency of neurological manifestations, including central nervous system (CNS) manifestations, in patients with coronavirus disease 2019 (COVID-19) pandemic is consistent with the virus's neurotropic nature. In most patients, brain magnetic resonance imaging (MRI) is a sensitive imaging modality in the diagnosis of viral encephalitides in the brain. The purpose of this study was to determine the frequency of brain lesion patterns on brain MRI in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia patients who developed focal and non-focal neurological manifestations. In addition, it will compare the impact of the Glasgow Coma Scale (GCS) as an index of deteriorating cerebral function on positive brain MRIs in both neurological manifestations. This retrospective study included an examination of SARS-CoV-2 pneumonia patients with real-time reverse transcription polymerase chain reaction (RT-PCR) confirmation, admitted with clinicoradiologic evidence of COVID-19 pneumonia, and who were candidates for brain MRI due to neurological manifestations suggesting brain involvement. Brain imaging acquired on a 3.0 T MRI system (Skyra; Siemens, Erlangen, Germany) with a 20-channel receive head coil. Brain MRI revealed lesions in 38 (82.6%) of the total 46 patients for analysis and was negative in the remaining eight (17.4%) of all finally enclosed patients with RT-PCR confirmed SARS-CoV-2 pneumonia. Twenty-nine (63%) patients had focal neurological manifestations, while the remaining 17 (37%) patients had non-focal neurological manifestations. The patients had a highly significant difference (p = 0.0006) in GCS, but no significant difference (p = 0.4) in the number of comorbidities they had. Brain MRI is a feasible and important imaging modality in patients with SARS-CoV-2 pneumonia who develop neurological manifestations suggestive of brain involvement, particularly in patients with non-focal manifestations and a decline in GCS.


Assuntos
Encefalopatias/etiologia , Encéfalo/diagnóstico por imagem , COVID-19/complicações , Adulto , Idoso , Encéfalo/patologia , Encefalopatias/diagnóstico por imagem , Encefalopatias/patologia , COVID-19/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , SARS-CoV-2/isolamento & purificação
8.
Bioorg Chem ; 115: 105208, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34365057

RESUMO

An array of newly synthesized thieno[3,2-d]pyrimidine-based derivatives and thienotriazolopyrimidines hybridized with some pharmacophoric anticancer fragments were designed, synthesized and assessed for their in vitro antiproliferative activity against MCF-7 and MDA-MB-231 breast cancer cell lines using erlotinib and pictilisib as reference standards in the MTT assay. In general, many compounds were endowed with considerable antiproliferative activity (IC50 = 0.43-1.31 µM). Some of the tested compounds, namely 3c, 5b, 5c, 9d, 10, 11b and 13 displayed remarkable antiproliferative activity against both cell lines. Meanwhile, compounds 2c-e, 3b, 4a, 5a, 9c and 15b showed noticeable selectivity against MCF-7 cells while compounds 2b, 3a, 4b, 6a-c, 7, 8, 9b and 12 exhibited considerable selectivity against MDA-MB-231 cells. Further mechanistic evidences for their anticancer activities were provided by screening the most potent compounds against MCF-7 and/or MDA-MB-231 cells for EGFR and ARO inhibitory activities using erlotinib and letrozole as reference standards respectively. Results proved that, in general, tested compounds were better EGFRIs than ARIs. In addition, significant overexpression in caspase-9 level in treated MCF-7 breast cell line samples was observed for all tested compounds with the 4-fluorophenylhydrazone derivative 2d exhibiting the highest activation. In treated MDA-MB-231 breast cell line samples, 11b was found to highly induce caspase-9 level thereby inducing apoptosis. Cell cycle analysis and Annexin V-FITC/PI assay were also assessed for active compounds where results indicated that all tested compounds induced preG1 apoptosis and cell cycle arrest at G2/M phase. Compound 9d, as an inhibitor of ARO, was observed to downregulate the downstream signaling proteins HSP27 and p-ERK in MCF-7 cells. Furthermore, compound 11b downregulated EGFR expression as well as the downstream signaling protein p-AKT. Docking experiments on EGFR and ARO enzymes supported their in vitro results. Thus, the thienotriazolopyrimidines 11b and 12 showing good EGFR inhibition and the thieno[3,2-d]-pyrimidine derivatives 3b and 9d, eliciting the best ARO inhibition activity, can be considered as new candidates as anti-breast cancer agents that necessitate further development.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Aromatase/metabolismo , Desenho de Fármacos , Inibidores de Proteínas Quinases/farmacologia , Pirimidinas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Feminino , Humanos , Estrutura Molecular , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Pirimidinas/síntese química , Pirimidinas/química , Relação Estrutura-Atividade
9.
Saudi Dent J ; 31(4): 469-475, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31695296

RESUMO

AIM: To histopathologically evaluate the pulpal healing after direct pulp capping with TotalFill and compared it with Neo MTA Plus in human tooth cultures. METHODS: Forty sound human premolars freshly extracted for orthodontic reasons were randomly assigned to two experimental groups; group I: TotalFill and group II: Neo MTA Plus. Standardized Class V cavities were prepared on the buccal surface of each tooth where the pulp exposure was performed with a dental explorer. The pulp-exposed teeth were immediately capped with one of the tested materials. The prepared cavities were then finally restored with glass-ionomer cement. Teeth were cultured for three weeks and three months. Then, the cultured teeth were demineralized, sectioned and stained for histopathological evaluation. Data collected and statistically analyzed by using Fisher's exact test. The significance level was set at P ≤ 0.05. RESULTS: Histopathological analysis showed complete dentin bridge formation and an absence of inflammatory pulp response. Statistical analysis showed no significant differences between the TotalFill and Neo MTA Plus groups during the observation periods. However, a significantly higher thickness of the dentin bridge was found in the group of teeth treated with TotalFill at three months. CONCLUSIONS: TotalFill produced similar favorable pulp healing and repair, and were comparable to Neo MTA Plus. Furthermore, TotalFill can form a thicker dentin bridge compared with Neo MTA Plus.

10.
Environ Technol ; 40(18): 2389-2399, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29558319

RESUMO

The aim of this study is to highlight the robustness and potentials of the anaerobic baffled reactor (ABR) configuration on keeping the microbial richness and diversity after starvation period of 7 days. The module at steady state operating conditions provided an average volumetric hydrogen production (VHP) of 0.2 ± 0.08 and 0.423 ± 0.5 l/d in the 1st and last compartment (C4). The VHP was gradually decreased from 0.2 to 0.003 l/d and from 0.423 to 0.1 l/d in compartments (C1 and C4) respectively during feed less period. However, the VHP was substantially increased up to 0.035 and 0.152 l/d in 1st (C1) and fourth compartment (C4) within 24 h, after reoperation of the ABR. Moreover, the H2 producers of Clostridiaceae, Ruminococcaceae, and Enterobacteriaceae families were dominant in the reactor after reoperation process. Quantitative polymerase chain reaction and next-generation sequencing methods results revealed that the microbial community structure was mainly composed of Proteobacteria, Firmicutes, Chloroflexi, Bacteroidetes, Planctomycetes, and Actinobacteria. The results showed the unique properties of the ABR configuration for keeping the microbial richness and diversity during feed less period.


Assuntos
Microbiota , Águas Residuárias , Anaerobiose , Reatores Biológicos , Hidrogênio , Eliminação de Resíduos Líquidos
11.
ACS Appl Mater Interfaces ; 10(25): 21103-21112, 2018 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-29906086

RESUMO

A new electrosynthetic approach for the fabrication of three-dimensional bicontinuous nanoporous platinum-based (3D-BC-NP-Pt(Au)) electrodes is described. Binary Pt-Ag alloys are first electrodeposited on gold substrates from appropriately formulated plating solutions. Following annealing and dealloying, a new family of nanoporous platinum-based electrodes emerges whose morphology, porosity, and chemical compositions depend on electrodeposition parameters and plating solution composition. Scanning electron microscopy images reveal an interesting and distinctive nanoporous gold-like microstructure with pores and ligaments in the 10-30 nm range arranged in a bicontinuous fashion throughout the thickness of the film. X-ray photoelectron spectroscopy (XPS) confirms that the as-formed electrodeposited films are silver-rich platinum binary alloys. Interestingly, XPS also reveals that after annealing and dealloying, the electrodes are actually ternary alloys containing platinum, gold, and a small amount of residual silver that remains after dealloying. Electrochemical measurements are consistent with this result and disclose a high surface area with roughness factors of 15-24. The ability to successfully conduct electrochemical measurements in biofouling solutions via a unique biosieving-like mechanism is demonstrated by exposure of the unique 3D bicontinuous nanoporous platinum-based electrode to fibrinogen in phosphate buffer and in a solution containing red blood cells. The work described herein has the potential to enrich the fields of electrochemical sensing and biosensing via the introduction of new 3D bicontinuous nanostructured porous platinum-based electrodes that can be easily and reliably fabricated.

12.
Bioorg Chem ; 77: 38-46, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29328997

RESUMO

New thienopyrimidinone and triazolothienopyrimidinone derivatives have been synthesized. These compounds were subjected to anti-inflammatory and antimicrobial activity screening aiming to identify new candidates that have dual anti-inflammatory and antimicrobial activities. Compounds 5, 7 and 10a showed minimal ulcerogenic effect and high selectivity towards human recombinant COX-2 over COX-1 enzyme. Their docking outcome correlated with their biological activity and assured the high selectivity binding towards COX-2. In addition, they could act safely up to 80 mg/kg orally or 40 mg/kg parentrally. The antimicrobial screening showed that compound 10a displayed distinctive inhibitory effect on the growth of Escherichia coli comparable to that of ampicillin. Moreover, compounds 5, 7, 9 and 12a possessed 50% of the inhibitory activity of ampicillin against E. coli. Thus, compounds 5, 7 and 10a represent promising dual acting anti-inflammatory and antimicrobial agents. This work provides rewarding template enriching the chemical space for dual anti-inflammatory anti-microbial activities.


Assuntos
Antibacterianos/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Antifúngicos/farmacologia , Inibidores de Ciclo-Oxigenase/farmacologia , Pirimidinas/farmacologia , Úlcera/tratamento farmacológico , Animais , Antibacterianos/síntese química , Antibacterianos/química , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/química , Antifúngicos/síntese química , Antifúngicos/química , Candida albicans/efeitos dos fármacos , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase/síntese química , Inibidores de Ciclo-Oxigenase/química , Relação Dose-Resposta a Droga , Escherichia coli/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Modelos Moleculares , Estrutura Molecular , Pirimidinas/síntese química , Pirimidinas/química , Ratos , Staphylococcus aureus/efeitos dos fármacos , Relação Estrutura-Atividade
13.
Future Med Chem ; 9(9): 881-897, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28635307

RESUMO

AIM: New triazolotetrahydrobenzothienopyrimidinone derivatives were synthesized. EXPERIMENTAL: Their structures were confirmed, and their anti-inflammatory, antimicrobial activities and ulcerogenic potentials were evaluated. RESULTS: Compounds 7a, 10a and 11a showed minimal ulcerogenic effect and high selectivity toward human recombinant COX-2 over COX-1 enzyme with IC50 values of 1.39, 1.22 and 0.56 µM, respectively. Their docking outcome correlated with their biological activity and confirmed the high selectivity binding toward COX-2. Compound 12b displayed antimicrobial activity comparable to that of ampicillin against Escherichia coli while compounds 6 and 11c were similar to ampicillin against Staphylococcus aureus. In addition, compounds 7a, 9a, 10b and 11c showed dual anti-inflammatory/antimicrobial activities. CONCLUSION: This work represents a promising matrix for developing new potential anti-inflammatory, antimicrobial and dual antimicrobial/anti-inflammatory candidates. [Formula: see text].


Assuntos
Antibacterianos/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Antiulcerosos/farmacologia , Antifúngicos/farmacologia , Animais , Antibacterianos/síntese química , Antibacterianos/química , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/química , Antiulcerosos/síntese química , Antiulcerosos/química , Antifúngicos/síntese química , Antifúngicos/química , Candida albicans/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Masculino , Testes de Sensibilidade Microbiana , Modelos Moleculares , Estrutura Molecular , Ratos , Ratos Sprague-Dawley , Staphylococcus aureus/efeitos dos fármacos , Úlcera Gástrica/tratamento farmacológico
14.
Eur J Med Chem ; 134: 52-61, 2017 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-28399450

RESUMO

Cardiovascular diseases (CVDs) are the main cause of deaths worldwide. Up-to-date, hypertension is the most significant contributing factor to CVDs. Recent clinical studies recommend calcium channel blockers (CCBs) as effective treatment alone or in combination with other medications. Being the most clinically useful CCBs, 1,4-dihydropyridines (DHPs) attracted great interest in improving potency and selectivity. However, the short plasma half-life which may be attributed to the metabolic oxidation to the pyridine-counterparts is considered as a major limitation for this class. Among the most efficient modifications of the DHP scaffold, is the introduction of biologically active N3-substituted dihydropyrimidine mimics (DHPMs). Again, some potent DHPMs showed only in vitro activity due to first pass effect through hydrolysis and removal of the N3-substitutions. Herein, the synthesis of new N3-substituted DHPMs with various functionalities linked to the DHPM core via two-carbon spacer to guard against possible metabolic inactivation is described. It was designed to keep close structural similarities to clinically efficient DHPs and the reported lead DHPMs analogues, while attempting to improve the pharmacokinetic properties through better metabolic stability. Applying whole batch clamp technique, five compounds showed promising L- and T- type calcium channel blocking activity and were identified as lead compounds. Structure requirements for selectivity against Cav1.2 as well against Cav3.2 are described.


Assuntos
Bloqueadores dos Canais de Cálcio/química , Bloqueadores dos Canais de Cálcio/farmacologia , Canais de Cálcio Tipo L/metabolismo , Di-Hidropiridinas/química , Di-Hidropiridinas/farmacologia , Bloqueadores dos Canais de Cálcio/síntese química , Cristalografia por Raios X , Di-Hidropiridinas/síntese química , Células HEK293 , Humanos , Hipertensão/tratamento farmacológico , Modelos Moleculares
15.
Bioorg Med Chem ; 25(6): 1926-1938, 2017 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-28233679

RESUMO

Low-voltage-activated calcium channels are important regulators of neurotransmission and membrane ion conductance. A plethora of intracellular events rely on their modulation. Accordingly, they are implicated in many disorders including epilepsy, Parkinson's disease, pain and other neurological diseases. Among different subfamilies, T-type calcium channels, and in particular the CaV3.2 isoform, were shown to be involved in nociceptive neurotransmission. The role of CaV3.2 in pain modulation was supported by demonstrating selective antisense oligonucleotide-mediated CaV3.2 knockdown, in vivo antinociceptive effects of T-type blockers, and pain attenuation in CaV3.2 knockout formalin-induced pain model. These Emerging investigations have provided new insights into targeting T-type calcium channels for pain management. Within this scope, various T-type calcium channel blockers have been developed such as mibefradil and ethosuximide. Although being active, most of these molecules interact with other receptors as well. This addresses the need for T-selectivity. Few selective T-type channel blockers of diverse chemical classes were developed such as ABT-639 and TTA-P2. Interestingly, R(-) efonidipine which is a dihydropyridine (DHP) showed T-channel selectivity. Systematic modification of 1,4-dihydropyridine scaffold introduced novel derivatives with 40-fold T-type selectivity over L-type calcium channels. Along these lines, substitution of the DHP core with various analogues favored T-selectivity and may serve as novel pharmacophores. Several dihydropyrimidine (DHPM) mimics were introduced by Squibb as potential candidates. As a continuation of this approach, the current study describes the synthesis of Novel N3 substituted DHPMs with structure similarities to the active DHPs. Different functional groups were introduced to the N3 position through a spacer to gain more information about activity and selectivity. Furthermore, the spacer aims at improving the metabolic stability of the molecules. Initial screening data by whole patch clamp technique showed a robust inhibition of Cav3.2 T-type channels by eleven compounds. Interestingly, four compounds of these were efficient selective T-type blockers. Based on selectivity and efficiency, two compounds were selected for in vivo evaluation in mouse models of inflammatory pain. Results showed effective attenuation of nociception and mechanical hypersensitivity.


Assuntos
Bloqueadores dos Canais de Cálcio/síntese química , Bloqueadores dos Canais de Cálcio/farmacologia , Modelos Animais de Doenças , Inflamação/tratamento farmacológico , Dor/tratamento farmacológico , Animais , Bloqueadores dos Canais de Cálcio/química , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Técnicas de Patch-Clamp , Espectroscopia de Prótons por Ressonância Magnética
16.
Appl Biochem Biotechnol ; 181(1): 142-156, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27507272

RESUMO

Multi-phase anaerobic reactor for H2 and CH4 production from paperboard mill wastewater was studied. The reactor was operated at hydraulic retention times (HRTs) of 12, 18, 24, and 36 h, and organic loading rates (OLRs) of 2.2, 1.5, 1.1, and 0.75 kg chemical oxygen demand (COD)/m3 day, respectively. HRT of 12 h and OLR of 2.2 kg COD/m3 day provided maximum hydrogen yield of 42.76 ± 14.5 ml/g CODremoved and volumetric substrate uptake rate (-rS) of 16.51 ± 4.43 mg COD/L h. This corresponded to the highest soluble COD/total COD (SCOD/TCOD) ratio of 56.25 ± 3.3 % and the maximum volatile fatty acid (VFA) yield (YVFA) of 0.21 ± 0.03 g VFA/g COD, confirming that H2 was mainly produced through SCOD conversion. The highest methane yield (18.78 ± 3.8 ml/g CODremoved) and -rS of 21.74 ± 1.34 mgCOD/L h were achieved at an HRT of 36 h and OLR of 0.75 kg COD/m3 day. The maximum hydrogen production rate (HPR) and methane production rate (MPR) were achieved at carbon to nitrogen (C/N) ratio of 47.9 and 14.3, respectively. This implies the important effect of C/N ratio on the distinction between the dominant microorganism bioactivities responsible for H2 and CH4 production.


Assuntos
Bactérias/metabolismo , Hidrogênio/química , Metano/química , Eliminação de Resíduos Líquidos , Anaerobiose , Bactérias/química , Reatores Biológicos , Resíduos Industriais , Metano/biossíntese , Nitrogênio/química , Águas Residuárias/química
17.
J Nanosci Nanotechnol ; 16(3): 2254-63, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27455626

RESUMO

Calcium phosphate cement (CPC) has been used for bone restoration despite its intrinsic fragile property. In order to enhance the CPC mechanical properties, biopolymers were introduced as filler to prepare CPC based cements. Chitosan/tetracalcium phosphate (TTCP)/dicalcium phosphate anhydrous (DCPA) based cement for bone repair has been prepared in the study. Solidification of the prepared cement was carried out in a simulate body fluid at 37 degrees C. The introduction of chitosan improved the mechanical performance of the as-prepared CPC hybrid nanocomposite. FTIR, SEM, TEM, HRTEM, XRD, and SAED were used to characterize the CPC nanocomposite. Data simulations have been performed to assist in determining the crystalline phase/s in the CPC hybrid nanocomposite. Based on the SAED, HRTEM measurements and data simulations, a monoclinic phase of hydroxyapatite (HAP) with a plate-like structure was obtained in the CPC system, which is believed to be responsible for the observed enhancement in CPC mechanical properties. The obtained composite has a biocompatibility comparable to that of commercial sample.


Assuntos
Biomimética , Cimentos Ósseos , Osso e Ossos/anormalidades , Durapatita/química , Teste de Materiais , Nanoestruturas , Fosfatos de Cálcio/química , Microscopia Eletrônica de Transmissão , Difração de Pó , Espectrometria por Raios X , Espectroscopia de Infravermelho com Transformada de Fourier
18.
Bioresour Technol ; 216: 520-8, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27268437

RESUMO

The effect of substrate to inoculum (So/Xo) ratio and supplementation of magnetite/graphene oxide (MGO) nano-composite material on hydrogen production from gelatinaceous wastewater via dark fermentation process was investigated. Results demonstrated that optimum So/Xo ratio of 1.0gCOD/gVSS achieved maximal hydrogen yield (HY) of 79.2±11.9mL H2/gCOD removed. Supplementation of anaerobes with 100mg/L MGO promoted HY up to 112.4±10.5mL H2/gCOD removed. Moreover, the degradation efficiency of carbohydrates, proteins and lipids was improved to 80.8±7.6, 34.4±2.3 and 31.4±2.2%, respectively. Acetate (HAc) and butyrate (HBu) concentrations increased from 102±6.8 to 125.3±6.3 and from 31.1±1.5 to 48.8±3.5mg/gVSS, respectively. However, propionate (HPr) concentration dropped from 35.9±2.7 to 15±1.3mg/gVSS. Hydrogenase enzyme activity increased 9-folds and the anaerobes elongated from ca. 1.8-2.9 to ca. 2.5-5.1µm with MGO addition. Moreover, Proteobacteria, Firmicutes, Clostridia and Bacilli were detected with the batches supplemented with MGO.


Assuntos
Biocombustíveis , Óxido Ferroso-Férrico/química , Grafite/química , Hidrogênio/metabolismo , Nanocompostos/química , Águas Residuárias/química , Acetatos/metabolismo , Bactérias Anaeróbias/genética , Bactérias Anaeróbias/metabolismo , Análise da Demanda Biológica de Oxigênio , Butiratos/metabolismo , Metabolismo dos Carboidratos , Fermentação , Óxido Ferroso-Férrico/metabolismo , Grafite/metabolismo , Metabolismo dos Lipídeos , Consórcios Microbianos/genética , Consórcios Microbianos/fisiologia , Óxidos/química , Óxidos/metabolismo , Proteínas/metabolismo , Eliminação de Resíduos Líquidos/instrumentação , Eliminação de Resíduos Líquidos/métodos
19.
Langmuir ; 32(23): 5925-36, 2016 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-27245273

RESUMO

Using a single-potential-step coelectrodeposition route, Ppy-SiO2 nanocomposite films characterized by a multimodal porous structure were cathodically deposited from ethanolic solutions on oxidizable and nonoxidizable substrates for the first time. The materials produced have an interesting and unique strata-like pore structure along their depth. With the exception of a silica-rich inner region, the nanocomposite films are homogeneous in composition. Because the region closest to the electrode surface is silica-rich, the fabrication of Ppy-SiO2 and Ppy free-standing films become possible using a multistep etching strategy. Such films can be captured on a variety of different supports depending on the application, and they maintain their conductivity when interfaced with an electrode surface. These mesoporous composite films form through a unique mechanism that involves the production of two catalysts, OH(-) and NO(+). Through the process of understanding the reaction mechanism, we highlighted the effect of two simultaneous competing redox reactions occurring at the electrode interface on the morphology of the electrodeposited Ppy nanocomposite films and how solvent can influence the Ppy electropolymerization reaction mechanism and hence control the morphology of the final material. In an ethanolic solvent system, the pyrrole monomers undergo a step-growth polymerization, and particulate-like nanostructured films were obtained even upon changing the monomer or acid concentration. In an aqueous-based system, nanowire-like structures were produced, which is consistent with a chain-growth mechanism. Such materials are promising candidates for a wide range of applications including electrochemical sensing, energy storage, and catalysis.

20.
Biosens Bioelectron ; 81: 294-302, 2016 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-26985581

RESUMO

Approaches to form flexible biosensors require strategies to tune materials for various biomedical applications. We report a facile approach using photolithography to fabricate poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) ( PEDOT: PSS) sensors on a fully biodegradable and flexible silk protein fibroin support. A benchtop photolithographic setup is used to fabricate high fidelity and high resolution PEDOT: PSS microstructures over a large (cm) area using only water as the solvent. Using the conductive micropatterns as working electrodes, we demonstrate biosensors with excellent electrochemical activity and stability over a number of days. The fabricated biosensors display excellent nonspecific detection of dopamine and ascorbic acid with high sensitivity. These devices are mechanically flexible, optically transparent, electroactive, cytocompatible and biodegradable. The benign fabrication protocol allows the conducting ink to function as a matrix for enzymes as shown by a highly sensitive detection of glucose. These sensors can retain their properties under repeated mechanical deformations, but are completely degradable under enzymatic action. The reported technique is scalable and can be used to develop sensitive, robust, and inexpensive biosensors with controllable biodegradability, leading to applications in transient or implantable bioelectronics and optoelectronics.


Assuntos
Técnicas Biossensoriais/instrumentação , Bombyx/química , Compostos Bicíclicos Heterocíclicos com Pontes/química , Técnicas Eletroquímicas/instrumentação , Polímeros/química , Poliestirenos/química , Seda/química , Animais , Ácido Ascórbico/análise , Biodegradação Ambiental , Dopamina/análise , Condutividade Elétrica , Enzimas Imobilizadas/química , Desenho de Equipamento , Glucose/análise , Maleabilidade
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