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1.
J Fluoresc ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38625574

RESUMO

Folic acid (FA) is a water-soluble vitamin found in diverse natural sources and is crucial for preserving human health. The risk of health issues due to FA deficiency underscores the need for a straightforward and sensitive FA detection methodology. Carbon dots (CDs) have gained significant attention owing to their exceptional fluorescence performance, biocompatibility, and easy accessibility. Consequently, numerous research studies have concentrated on developing advanced CD fluorescent probes to enable swift and precise FA detection. Despite these efforts, there is still a requirement for a thorough overview of the efficient synthesis of CDs and their practical applications in FA detection to further promote the widespread use of CDs. This review paper focuses on the practical applications of CD sensors for FA detection. It begins with an in-depth introduction to FA and CDs. Following that, based on various synthetic approaches, the prepared CDs are classified into diverse detection methods, such as single sensing, visual detection, and electrochemical methods. Furthermore, persistent challenges and potential avenues are highlighted for future research to provide valuable insights into crafting effective CDs and detecting FA.

2.
Environ Res ; 252(Pt 1): 118862, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38574984

RESUMO

The escalating issue of air pollution has become a significant concern in urban regions, including Islamabad, Pakistan, due to the rise in air pollutant emissions driven by economic and industrial expansion. To gain a deeper understanding of air pollution, a study was conducted during winter 2022-2023, assessing physical, chemical, and biological factors in Islamabad. The findings revealed that the average concentration of fine particulate matter (PM2.5) was notably greater than the World Health Organization (WHO) guidelines, reaching 133.39 µg/m³. Additionally, the average concentration of bacteria (308.64 CFU/m³) was notably greater than that of fungi (203.55 CFU/m³) throughout the study. Analytical analyses, including SEM-EDS and FTIR, showed that the PM2.5 in Islamabad is composed of various particles such as soot aggregates, coal fly ash, minerals, bio-particles, and some unidentified particles. EF analysis distinguished PM2.5 sources, enhancing understanding of pollutants origin, whereas Spearman's correlation analysis elucidated constituent interactions, further explaining air quality impact. The results from the Inductively Coupled Plasma Atomic Emission Spectroscopy (ICP-OES) indicated a gradual increase in the total elemental composition of PM2.5 from autumn to winter, maintaining high levels throughout the winter season. Furthermore, a significant variation was found in the mass concentration of PM2.5 when comparing samples collected in the morning and evening. The study also identified the presence of semi-volatile organic compounds (SVOCs) in PM2.5 samples, including polycyclic aromatic hydrocarbons (PAHs) and phenolic compounds, with notable variations in their concentrations. Utilizing health risk assessment models developed by the US EPA, we estimated the potential health risks associated with PM2.5 exposure, highlighting the urgency of addressing air quality issues. These findings provide valuable insights into the sources and composition of PM2.5 in Islamabad, contributing to a comprehensive understanding of air quality and its potential environmental and health implications.


Assuntos
Poluentes Atmosféricos , Material Particulado , Material Particulado/análise , Paquistão , Poluentes Atmosféricos/análise , Humanos , Monitoramento Ambiental , Cidades , Tamanho da Partícula , Poluição do Ar/análise
3.
Am J Emerg Med ; 76: 41-47, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37988980

RESUMO

BACKGROUND: The choice of fluid resuscitation in Traumatic Hemorrhagic shock (THS) remains a critical aspect of patient management. Bicarbonated Ringers solution (BRS) has shown promise due to its composition resembling human Extracellular Fluid and its potential benefits on hemodynamics. OBJECTIVE: To evaluate the efficacy, mortality rates, hemodynamic effects, and adverse outcomes of Sodium Bicarbonate Ringer's Solution in the treatment of hemorrhagic shock, as compared to other relevant interventions. METHOD: A comprehensive examination of the available literature was performed by conducting systematic searches in prominent databases such as Cochrane, EMBASE, MEDLINE, and PubMed. The process employed predefined criteria to extract relevant data and evaluate the quality of the studies. The outcome measures considered encompassed survival rates, mortality, mean arterial pressure (MAP), heart rate (HR), and adverse events. RESULT: The meta-analysis of three studies showed that compared to the other crystalloids, the use of BRS had an odds ratio for survival of 1.86 (95% CI: 0.94, 3.71; p = 0.08; I2 = 0%), an odds ratio for total adverse events of 0.14 (95% CI: 0.06, 0.35; p < 0.0001; I2 = 22%), a mean difference in heart rate of -4.49 (95% CI: -7.55, -1.44; p = 0.004; I2 = 13%), and a mean difference in mean arterial pressure of 2.31 (95% CI: -0.85, 5.47; p = 0.15; I2 = 66%). CONCLUSION: BRS demonstrated a significant reduction in complications, including adult respiratory distress syndrome (ARDS), Multiple Organ Dysfunction (MODS), and Total Adverse Effects, when compared to other solutions in the treatment of THS. Additionally, THS patients resuscitated with BRS experienced a notable decrease in heart rate. The findings suggest BRS may contribute to organ stability and potential survival improvement due to its similarity to human Extracellular Fluid and minimal impact on the liver.


Assuntos
Choque Hemorrágico , Humanos , Choque Hemorrágico/tratamento farmacológico , Choque Hemorrágico/complicações , Solução de Ringer , Soluções Cristaloides/uso terapêutico , Bicarbonato de Sódio , Soluções Isotônicas/uso terapêutico , Hemorragia/complicações , Ressuscitação/métodos
4.
Am J Emerg Med ; 78: 188-195, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38301369

RESUMO

OBJECTIVE: This study aimed to assess the impact of establishing a pre-hospital definitive airway on mortality and morbidity compared with no prehospital airway in cases of severe traumatic brain injury (TBI). BACKGROUND: Traumatic brain injury (TBI) is a global health concern that is associated with substantial morbidity and mortality. Prehospital intubation (PHI) has been proposed as a potential life-saving intervention for patients with severe TBI to mitigate secondary insults, such as hypoxemia and hypercapnia. However, their impact on patient outcomes remains controversial. METHODS: A systematic review and meta-analysis were conducted to assess the effects of prehospital intubation versus no prehospital intubation on morbidity and mortality in patients with severe TBI, adhering to the PRISMA guidelines. RESULTS: 24 studies, comprising 56,543 patients, indicated no significant difference in mortality between pre-hospital and In-hospital Intubation (OR 0.89, 95% CI 0.65-1.23, p = 0.48), although substantial heterogeneity was noted. Morbidity analysis also showed no significant difference (OR 0.83, 95% CI 0.43-1.63, p = 0.59). These findings underscore the need for cautious interpretation due to heterogeneity and the influence of specific studies on the results. CONCLUSION: In summary, an initial assessment did not reveal any apparent disparity in mortality rates between individuals who received prehospital intubation and those who did not. However, subsequent analyses and randomized controlled trials (RCTs) demonstrated that patients who underwent prehospital intubation had a reduced risk of death and morbidity. The dependence on biased observational studies and the need for further replicated RCTs to validate these findings are evident. Despite the intricacy of the matter, it is crucial to intervene during severe airway impairment.


Assuntos
Manuseio das Vias Aéreas , Lesões Encefálicas Traumáticas , Serviços Médicos de Emergência , Intubação Intratraqueal , Humanos , Lesões Encefálicas Traumáticas/terapia , Lesões Encefálicas Traumáticas/mortalidade , Serviços Médicos de Emergência/métodos , Manuseio das Vias Aéreas/métodos , Intubação Intratraqueal/métodos
5.
Acta Neurochir (Wien) ; 166(1): 121, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38436794

RESUMO

OBJECTIVE: Acute subdural hematoma (ASDH) stands as a significant contributor to morbidity after severe traumatic brain injuries (TBI). The primary treatment approach for patients experiencing progressive neurological deficits or notable mass effects is the surgical removal of the hematoma, which can be achieved through craniotomy (CO) or decompressive craniectomy (DC). Nevertheless, the choice between these two procedures remains a subject of ongoing debate and controversy. MATERIALS AND METHODS: We conducted a comprehensive literature review, utilizing prominent online databases and manually searching references related to craniotomy and craniectomy for subdural hematoma evacuation up to November 2023. Our analysis focused on outcome variables such as the presence of residual subdural hematoma, the need for revision procedures, and overall clinical outcomes. RESULTS: We included a total of 11 comparative studies in our analysis, encompassing 4269 patients, with 2979 undergoing craniotomy and 1290 undergoing craniectomy, meeting the inclusion criteria. Patients who underwent craniectomy displayed significantly lower scores on the Glasgow Coma Scale (GCS) during their initial presentation. Following surgery, the DC group exhibited a significantly reduced rate of residual subdural (P = 0.009). Additionally, the likelihood of a poor outcome during follow-up was lower in the CO group. Likewise, the mortality rate was lower in the CO group compared to the craniectomy group (OR 0.63, 95% CI 0.41-0.98, I2 = 84%, P = 0.04). CONCLUSION: Our study found that CO was associated with more favorable outcomes in terms of mortality, reoperation rate, and functional outcome while DC was associated with less likelihood of residual subdural hematoma. Upon further investigation of patient characteristics who underwent into either of these interventions, it was very clear that patients in DC cohort have more serious and low pre-op characteristics than the CO group. Nonetheless, brain herniation and advanced age act as independent factor for predicting the outcome irrespective of the intervention.


Assuntos
Lesões Encefálicas Traumáticas , Craniectomia Descompressiva , Hematoma Subdural Agudo , Humanos , Hematoma Subdural Agudo/cirurgia , Hematoma Subdural , Bases de Dados Factuais
6.
Chem Biodivers ; : e202401775, 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39161231

RESUMO

This study explores the capability of thiazoles as potent inhibitors of SARS-CoV-2 Mpro. Seventeen thiazoles (1-17) were screened for their linking affinity with the active site of SARS-CoV-2 Mpro and compared with the FDA-recommended antiviral drugs, Remdesivir and Baricitinib. Density Functional Theory (DFT) calculations provided electronic and energetic properties of these ligands, shedding light on their stability and reactivity. Molecular docking analysis revealed that thiazole derivatives exhibited favorable linking affinities with various functional sites of SARS-CoV-2 proteins, including spike receptor-linking zone, nucleocapsid protein N-terminal RNA linking zone, and Mpro. Notably, compounds 3, 10, and 12 displayed the best interaction with 6LZG as compared to FDA-approved antiviral drugs Remdesivir and Baricitinib, while compounds 1, 10, and 8 exhibited strong linking with 6M3M and also better than Remdesivir and Baricitinib. Additionally, compounds 3, 1, and 6 showed promising interactions with 6LU7 but only compound 3 performed better than Baricitinib. An ADME (Absorption, Distribution, Metabolism, and Excretion) study provided insights into the pharmacokinetics and drug-likeness of these compounds, with all ligands demonstrating good physicochemical characteristics, lipophilicity, water solubility, pharmacokinetics, drug-likeness, and medicinal chemistry attributes. The results suggest that these selected thiazole derivatives hold promise as potential candidates for further drug development.

7.
J Enzyme Inhib Med Chem ; 38(1): 2163394, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36629454

RESUMO

Deposition of hydroxyapatite (HA) or alkaline phosphate crystals on soft tissues causes the pathological calcification diseases comprising of end-stage osteoarthritis (OA), ankylosing spondylitis (AS), medial artery calcification and tumour calcification. The pathological calcification is symbolised by increased concentration of tissue non-specific alkaline phosphatase (TNAP). An efficient therapeutic strategy to eradicate these diseases is required, and for this the alkaline phosphatase inhibitors can play a potential role. In this context a series of novel quinolinyl iminothiazolines was synthesised and evaluated for alkaline phosphatase inhibition potential. All the compounds were subjected to DFT studies where N-benzamide quinolinyl iminothiazoline (6g), N-dichlorobenzamide quinolinyl iminothiazoline (6i) and N-nitrobenzamide quinolinyl iminothiazoline (6j) were found as the most reactive compounds. Then during the in-vitro testing, the compound N-benzamide quinolinyl iminothiazoline (6g) exhibited the maximum alkaline phosphatase inhibitory effect (IC50 = 0.337 ± 0.015 µM) as compared to other analogues and standard KH2PO4 (IC50 = 5.245 ± 0.477 µM). The results were supported by the molecular docking studies, molecular dynamics simulations and kinetic analysis which also revealed the inhibitory potential of compound N-benzamide quinolinyl iminothiazoline (6g) against alkaline phosphatase. This compound can be act as lead molecule for the synthesis of more effective inhibitors and can be suggested to test at the molecular level.


Assuntos
Fosfatase Alcalina , Inibidores Enzimáticos , Simulação de Acoplamento Molecular , Cinética , Fosfatase Alcalina/metabolismo , Inibidores Enzimáticos/química , Benzamidas/farmacologia
8.
Neurosurg Rev ; 47(1): 12, 2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38091115

RESUMO

BACKGROUND: Trigeminal neuralgia (TN) is a chronic condition characterized by intense facial pain akin to electric shocks, often associated with the trigeminal nerve. It can be either idiopathic or secondary, with multiple sclerosis (Ms) being a significant contributing factor. Non-responsive patients may opt for minimally invasive procedures, such as gamma knife radiosurgery (GKRS), which offers precise, non-invasive treatment and is frequently chosen as a primary approach. This meta-analysis evaluates the long-term efficacy of GKRS in TN management in Ms patients. METHODS: We conducted a focused search across various databases. Inclusion criteria encompassed studies with ≥ 30 patients using GKRS for TN in Ms, reporting pertinent clinical outcomes. Primary outcomes assessed GKRS efficacy through Barrow Neurological Institute Pain scores. Secondary outcomes encompassed bothersome numbness, facial numbness, and recurrence. Data analysis employed OpenMeta, random effect models, and odds ratios with 95% confidence intervals. Heterogeneity was assessed using I2 statistics. RESULTS: Fourteen studies with 752 cases of GKRS for TN were included. Regarding the outcomes, 83% of patients experienced a positive initial pain response, while the overall treatment success rate was 51%. Additionally, 19.6% of patients reported facial numbness, 4.1% experienced bothersome numbness, and 40% faced recurrence. The odds ratio for positive initial pain response was 0.83 (95% CI, 0.76-0.89), while for treatment success, it was 0.51 (95% CI, 0.379-0.639). Facial numbness had an odds ratio of 0.196 (95% CI, 0.130-0.262), bothersome numbness had an odds ratio of 0.041 (95% CI, 0.013-0.069), and recurrence had an odds ratio of 0.403 (95% CI, 0.254-0.551). CONCLUSIONS: In conclusion, treating trigeminal neuralgia in multiple sclerosis patients remains challenging. GKRS shows promise, but customized treatment approaches tailored to individual patient characteristics are urgently needed to address the unique challenges of this condition.


Assuntos
Esclerose Múltipla , Radiocirurgia , Neuralgia do Trigêmeo , Humanos , Neuralgia do Trigêmeo/cirurgia , Radiocirurgia/métodos , Esclerose Múltipla/complicações , Esclerose Múltipla/cirurgia , Hipestesia/complicações , Hipestesia/cirurgia , Resultado do Tratamento , Dor/cirurgia , Estudos Retrospectivos , Seguimentos
9.
Molecules ; 28(15)2023 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-37570800

RESUMO

The present study reports the one-step synthesis of several 3-formyl-4-hydroxycouramin-derived enamines (4a-4i) in good yields (65-94%). The characterization of the synthesized compounds was carried out via advanced analytical and spectroscopic techniques, such as melting point, electron impact mass spectrometry (EI-MS), 1H-NMR, 13C-NMR, elemental analysis, FTIR, and UV-Visible spectroscopy. The reaction conditions were optimized, and the maximum yield was obtained at 3-4 h of reflux of the reactants, using 2-butanol as a solvent. The potato disc tumor assay was used to assess Agrobacterium tumefaciens-induced tumors to evaluate the anti-tumor activities of compounds (4a-4i), using Vinblastine as a standard drug. The compound 4g showed the lowest IC50 value (1.12 ± 0.2), which is even better than standard Vinblastine (IC50 7.5 ± 0.6). For further insight into their drug actions, an in silico docking of the compounds was also carried out against the CDK-8 protein. The binding energy values of compounds were found to agree with the experimental results. The compounds 4g and 4h showed the best affinities toward protein, with a binding energy value of -6.8 kcal/mol.


Assuntos
4-Hidroxicumarinas , Antineoplásicos , Estrutura Molecular , Relação Estrutura-Atividade , Vimblastina , Simulação de Acoplamento Molecular , Antineoplásicos/química
10.
Environ Res ; 212(Pt A): 113138, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35364043

RESUMO

Recent trends in adsorption of Chromium (Cr), Copper (Cu), Lead (Pb) and Mercury (Hg) in wastewater using (i) carbonaceous materials including activated carbon (AC) and biochar (BC), and (ii) nanomaterials including nano zero-valent iron (nZVI) and MXenes have been discussed in this paper. It has been found that adsorption capacity depends largely on the adsorbent modification technique, initial pH of wastewater, dosage of adsorbent, contact time and initial concentration of the pollutants. The pH value ranges for maximum removal of Cr, Cu, Pb and Hg have been reported as 2-4, 5-6, 5-8 and 3-8, respectively. Up to 99% removal of metals has been reported using AC, BC, nZVI and MXene. The mechanism involves the reduction and chemical adsorption of metals. AC and BC have a higher surface area (up to 5000 m2/g) compared to nZVI (up to 500 m2/g) and MXene (up to 67.66 m2/g). However, the higher reactivity and regeneration capacity of nZVI and MXene make them suitable adsorbents. From a practical point of view the application of adsorbents for real effluents, cost analysis, regeneration capability and reuse of heavy metals are some aspects that need attention in future studies. The removal efficiencies of AC and BC are comparable to the nZVI and MXene. The cost analysis may be an attractive aspect to decide the future application of these adsorbents at large scale.


Assuntos
Mercúrio , Nanoestruturas , Poluentes Químicos da Água , Adsorção , Carvão Vegetal , Cromo/análise , Cobre/análise , Íons/análise , Ferro/análise , Chumbo/análise , Mercúrio/análise , Águas Residuárias/análise , Água/análise , Poluentes Químicos da Água/análise
11.
Sensors (Basel) ; 22(8)2022 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-35459008

RESUMO

This paper presents the LC-type passive wireless sensing system for the simultaneous and independent detection of triple parameters, featuring three different capacitive sensors controlled by two mechanical switches. The sensor coil was connected with three different capacitors in parallel and two mechanical switches were in series between every two capacitors, which made the whole system have three resonant frequencies. The readout coil was magnetically coupled with the sensor coil to interrogate the sensor wirelessly. The circuit was simulated advanced design system (ADS) software, and the LC sensor system was mathematically analyzed by MATLAB. Results showed that the proposed LC sensing system could test three different capacitive sensors by detecting three different resonant frequencies. The sensitivity of sensors could be determined by the capacitance calculated from the detected resonant frequencies, and the resolution of capacitance was 0.1 PF and 0.2 PF when using the proposed sensor system in practical applications. To validate the proposed scheme, a PCB inductor and three variable capacitors were constructed with two mechanical switches to realize the desired system. Experimental results closely verified the simulation outputs.


Assuntos
Tecnologia sem Fio , Capacitância Elétrica
12.
Sensors (Basel) ; 22(7)2022 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-35408407

RESUMO

With the recent development in power electronic devices, HVDC (High Voltage Direct Current) systems have been recognized as the most prominent solution to transmit electric power economically. Today, several HVDC projects have been implemented physically. The conventional HVDC systems use grid commutation converters, and its commutation relies on an AC system for the provision of voltage. Due to this reason, there are possibilities of commutation failure during fault. Furthermore, once the DC (Direct Current) system power is interrupted momentarily, the reversal of work power is likely to cause transient over-voltage, which will endanger the safety of power grid operation. Hence, it is necessary to study the commutation failure and transient over-voltage issues. To tackle the above issues, in this paper, the dynamic and transient characteristics of Pakistan's first HVDC project, i.e., the Matiari-Lahore ±660 kV transmission line has been analyzed in an electromagnetic transient model of PSCAD/EMTDC. Based on the characteristics of the DC and the off-angle after the failure, a new control strategy has been proposed. The HVDC system along with its proposed control strategy has been tested under various operating conditions. The proposed controller increases the speed of fault detection, reduces the drop of AC voltage and DC and suppresses the commutation failure probability of LCC-HVDC (line commutated converter- high voltage direct current).

13.
Int J Mol Sci ; 23(22)2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36430579

RESUMO

Emotional stress is believed to be associated with increased tumor progression. Stress-induced epigenetic modifications can contribute to the severity of disease and poor prognosis in cancer patients. The current study aimed to investigate the expression profiles along with the prognostic significance of psychological stress-related genes in metastatic breast cancer patients, to rationalize the molecular link between emotional stress and cancer progression. We profiled the expression of selected stress-associated genes (5-HTT, NR3C1, OXTR, and FKBP5) in breast cancer including the stress evaluation of all participants using the Questionnaire on Distress in Cancer Patients-short form (QSC-R10). A survival database, the Kaplan-Meier Plotter, was used to explore the prognostic significance of these genes in breast cancer. Our results showed relatively low expressions of 5-HTT (p = 0.02) and OXTR (p = 0.0387) in metastatic breast cancer patients as compared to the non-metastatic group of patients. The expression of NR3C1 was low in tumor grade III as compared to grade II (p = 0.04). Additionally, the expression of NR3C1 was significantly higher in patients with positive estrogen receptor status. However, no significant difference was found regarding FKBP5 expression in breast cancer. The results suggest a potential implication of these genes in breast cancer pathology and prognosis.


Assuntos
Neoplasias da Mama , Angústia Psicológica , Humanos , Feminino , Neoplasias da Mama/metabolismo , Prognóstico , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , RNA Mensageiro/genética
14.
Cardiol Young ; 31(6): 1043-1047, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33504377

RESUMO

Coronary artery aneurysms in children were observed as a rare complication associated with coronavirus disease 2019 (COVID-19). This case report describes the severe end of the spectrum of the new multisystem inflammatory syndrome in a 12-year-old child with coronary aneurysms, myocardial dysfunction, and shock, managed successfully with extracorporeal membrane oxygenation support and immunomodulation therapy. This report also highlights the additional benefits of cardiac CT in the diagnosis and follow-up of coronary aneurysms.


Assuntos
COVID-19 , Aneurisma Coronário , Oxigenação por Membrana Extracorpórea , Criança , Aneurisma Coronário/diagnóstico por imagem , Aneurisma Coronário/etiologia , Humanos , Imunomodulação , SARS-CoV-2 , Síndrome de Resposta Inflamatória Sistêmica , Tomografia Computadorizada por Raios X
15.
Appl Opt ; 59(34): 10826-10837, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33361903

RESUMO

This paper presents multi-path, two-photon excitation cross-section calculations for krypton, using first-order perturbation theory. For evaluation of the two-photon-transition matrix element, this paper formulates the two-photon cross-section calculation as a matrix mechanics problem. From a finite basis of states, consisting of 4p, 5s, 6s, 7s, 5p, 6p, 4d, 5d, and 6d orbitals, electric dipole matrix elements are constructed, and a Green's function is expressed as a truncated, spectral expansion of solutions, satisfying the Schrödinger equation. Electric dipole matrix elements are evaluated via tabulated oscillator strengths, and where those are unavailable, quantum-defect theory is used. The relative magnitudes of two-photon cross-sections for eight krypton lines in the 190-220 nm range are compared to experimental excitation spectra with good agreement. This work provides fundamental physical understanding of the Kr atom, which adds to experimental observations of relative fluorescence intensity. This is valuable when comparing excitation schemes in different environments for krypton fluorescence experiments. We conclude that two-photon excitation at 212.556 nm is optimal for single-laser, krypton tagging velocimetry or krypton planar laser-induced fluorescence.

16.
Microb Pathog ; 136: 103653, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31398527

RESUMO

Pneumococcal strains are variably resistant to killing by neutrophil extracellular traps (NETs). We hypothesize that this variability in resistance is due to heterogeneity in pneumococcal surface protein A (PspA), a structurally diverse virulence factor of Streptococcus pneumoniae. Pneumococcal strains showed variability in induction of NETs and in susceptibility to killing by NETs. The variability in susceptibility to NETs-mediated killing of pneumococcal strains is attributed to PspA, as strains lacking the surface expression of PspA were significantly more sensitive to NETs-mediated killing compared to the wild-type strains. Using pspA switch mutants we were further able to demonstrate that NETs induction and killing by NETs is a function of PspA as mutants with switch PspA demonstrated donor phenotype. Antibody to PspA alone showed an increase in induction of NETs, and NETs thus generated were able to trap and kill pneumococci. Pneumococci opsonized with antibody to PspA showed increase adherence to NETs but a decrease susceptibility to killing by NETs. In conclusion we demonstrate a novel role for pneumococcal PspA in resisting NETs mediated killing and allowing the bacteria to escape containment by blocking binding of pneumococci to NETs.


Assuntos
Proteínas de Bactérias/metabolismo , Armadilhas Extracelulares/metabolismo , Evasão da Resposta Imune , Viabilidade Microbiana , Streptococcus pneumoniae/imunologia , Streptococcus pneumoniae/fisiologia , Células Cultivadas , Humanos
18.
Bioorg Chem ; 90: 103063, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31220666

RESUMO

The enzyme tyrosinase plays a vital role in melanin biosynthesis and enzymatic browning of vegetables and fruits. A series of novel quinolinyl thiourea analogues (11a-j) were synthesized by reaction of 3-aminoquinoline and corresponding isothiocyanates, in moderate to excellent yields with different substitutions and their inhibitory effect on mushroom tyrosinase and free radical scavenging activity were evaluated. The compound N-(quinolin-3-ylcarbamothioyl)hexanamide (11c) exhibited the maximum tyrosinase inhibitory effect (IC50 = 0.0070 ±â€¯0.0098 µM) compared to other derivatives and the reference Kojic acid (IC50 = 16.8320 ±â€¯0.0621 µM). The docking studies were carried out and the compound (11c) showed most negative estimated free energy of -7.2 kcal/mol in mushroom tyrosinase active site. The kinetic analysis revealed that the compound (11c) inhibits the enzyme tyrosinase non-competitively to form the complex of enzyme and inhibitor. The results revealed that 11c could be identified as putative lead compound for the design of efficient tyrosinase inhibitors.


Assuntos
Agaricales/enzimologia , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacologia , Sequestradores de Radicais Livres/síntese química , Sequestradores de Radicais Livres/farmacologia , Monofenol Mono-Oxigenase/antagonistas & inibidores , Tioureia/química , Humanos , Cinética , Modelos Moleculares , Simulação de Acoplamento Molecular , Estrutura Molecular , Monofenol Mono-Oxigenase/química , Conformação Proteica , Relação Estrutura-Atividade
20.
Pak J Pharm Sci ; 31(3): 967-971, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29716881

RESUMO

COPD is a complicated disease. Current available treatments are just for symptomatic relief and they cannot reverse the damages to lungs tissues due to alveolar destruction in COPD. Research is being conducted to evaluate new treatments and strategies to find specific treatments to minimize the symptoms of COPD. A new mixture of herbal medicine i.e AKL1 has emerged and thought to cure COPD symptoms especially cough related quality of life of COPD patients. Although, the results have showed no significant difference as compared to placebo but researchers recommend further evaluation in a large population (COPD Patients) group. Another medicine Roflumilast, a phosphodiesterase 4 inhibitor, was also found to be effective to treat COPD under specific recommendations with further research needed. Finally another medicine Indacaterol, a novel, once-daily (o.d) inhaled long-acting ß2-agonist proved to be effective clinically to treat COPD related broncho-constriction and also increasing the COPD patient's compliance by reducing the number of doses as compared to other conventional inhaled bronchodilators such as Albuterol.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Broncodilatadores/administração & dosagem , Inibidores da Fosfodiesterase 4/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Administração por Inalação , Aminopiridinas/administração & dosagem , Benzamidas/administração & dosagem , Ciclopropanos/administração & dosagem , Humanos , Indanos/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Quinolonas/administração & dosagem , Resultado do Tratamento
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