Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 114
Filtrar
2.
Artigo em Inglês | MEDLINE | ID: mdl-34515019

RESUMO

AIM: The aim of the present work was to evaluate the neuroprotective potential of berberine, levetiracetam and their combination in lead acetate induced neurotoxicity by applying a drug repositioning approach. BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disease characterized by impairment of memory, disturbances in reasoning, planning, language and perception. Currently, there are only four drugs approved by US-FDA for AD; therefore, there is an extensive need for new drug development. The drug repositioning approach refers to the development of new uses for existing or abandoned pharmaceuticals. Several studies support the neuroprotective abilities of anti-oxidants resulting in neuronal protection against neurotoxins, suppression of oxidative stress and promotion of memory, learning and cognitive functions. Many natural polyphenols are being investigated as a potential therapeutic option for AD. Levetiracetam (LEV), a second-generation antiepileptic drug, is a new molecule that is clearly differentiated from conventional antiepileptic drugs by its pharmacologic properties. LEV also has been previously demonstrated to protect against oxidative stress-induced neurotoxicity in several models of seizures. Berberine (BBR) is an anti-inflammatory and anti-oxidant phytoconstituent. OBJECTIVE: To study the therapeutic effect of berberine, levetiracetam and their physical mixture in lead acetate-induced neurotoxicity in Swiss albino mice for probable application in the management of Alzheimer's disease. METHODS: Neurotoxicity was induced in Swiss albino mice by lead acetate. Behavioural parameters, such as transfer latency time and percentage alternation, were studied using Morris water maze (MWM), Elevated plus-maze test (EPM) and Y- maze for the assessment of improvement in learning and memory. Concentrations of acetylcholinesterase, MDA and GSH in the brain were also estimated. Brain samples were subjected to histopathological studies. RESULTS: Results revealed that the combination of BBR and LEV exhibited a significant neuroprotective effect by decreasing escape latency time and increasing time spent in the target quadrant in MWM. The combination also decreases transfer latency time in EPM and acetylcholinesterase levels in the brain as compared to standard donepezil. Reduced neuronal damage was also confirmed by the histopathological report. CONCLUSION: Leveteracitam, berberin and their combination resulted in the significant conservation of various behavioural, biochemical, enzymatic and anti-oxidant parameters that were evaluated. The neuroprotective effect of plain leveteracitam and berberin was significantly better than their combination. However, the anticipated synergism or additive effect was not observed with a combination of leveteracitam and berberin in lead acetate-induced neurotoxicity.

3.
BMJ Open Qual ; 10(Suppl 1)2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34344746

RESUMO

BACKGROUND: Unintended pregnancies have a negative impact on the health and economy of a nation, which can be prevented by effective family planning (FP) services. Postpartum intrauterine device (PPIUCD) is a safe and effective FP method which allows women to obtain long-acting contraception before discharge from the point of delivery. We observed poor coverage of deliveries with PPIUCD at our facility. This was the trigger to initiate a quality improvement (QI) initiative to increase the PPIUCD coverage from current rate of 4.5%-10% in 3-month period. METHOD: A fishbone analysis of the problem was done and the following causes were identified: lack of focused counselling for FP, lack of sensitisation and training of resident doctors and inconsistent supply of intrauterine contraceptive devices (IUCDs). A QI team was constituted with representatives from faculty members, residents, interns, nursing officers and FP counsellors. The point of care quality improvement methodology was used. INTERVENTIONS: Daily counselling of antenatal women was started by the counsellors and interns in antenatal wards. A WhatsApp group of residents was made initially to sensitise them; and later for parking of problems and trouble shooting. The residents were provided hands-on training at skills lab. Uninterrupted supply of IUCDs was ensured by provision of buffer stock of IUCDs with respective store keepers. RESULT: The PPIUCD insertion rates improved from 4.5% to 19.2% at 3 months and have been sustained to a current 30%-35% after 1 ½ years of initiation of the project tiding through the turbulence during the COVID-19 pandemic using QI techniques. CONCLUSION: Sensitisation and training of residents as well as creation of awareness among antenatal women through targeted counselling helped improve PPIUCD coverage at the facility. QI initiatives have the potential to facilitate effective implementation of the FP programmes by strategic utilisation of the resources.


Assuntos
Anticoncepção , Serviços de Planejamento Familiar , Dispositivos Intrauterinos , Período Pós-Parto , Melhoria de Qualidade , Adulto , COVID-19 , Anticoncepção/estatística & dados numéricos , Aconselhamento , Feminino , Pessoal de Saúde , Humanos , Índia , Pandemias , Aceitação pelo Paciente de Cuidados de Saúde , Alta do Paciente , Gravidez
4.
J Biomol Struct Dyn ; : 1-24, 2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34253149

RESUMO

A new series of quinoline derivatives has been designed and synthesized as probable protease inhibitors (PIs) against severe acute respiratory syndrome coronavirus 2. In silico studies using DS v20.1.0.19295 software have shown that these compounds behaved as PIs while interacting at the allosteric site of target Mpro enzyme (6LU7). The designed compounds have shown promising docking results, which revealed that all compounds formed hydrogen bonds with His41, His164, Glu166, Tyr54, Asp187, and showed π-interaction with His41, the highly conserved amino acids in the target protein. Toxicity Prediction by Komputer Assisted Technology results confirmed that the compounds were found to be less toxic than the reference drug. Further, molecular dynamics simulations were performed on compound 5 and remdesivir with protease enzyme. Analysis of conformational stability, residue flexibility, compactness, hydrogen bonding, solvent accessible surface area (SASA), and binding free energy revealed comparable stability of protease:5 complex to the protease: remdesivir complex. The result of hydrogen bonding showed a large number of intermolecular hydrogen bonds formed between protein residues (Glu166 and Gln189) and ligand 5, indicating strong interaction, which validated the docking result. Further, compactness analysis, SASA and interactions like hydrogen-bonding demonstrated inhibitory properties of compound 5 similar to the existing reference drug. Thus, the designed compound 5 might act as a potential inhibitor against the protease enzyme.Communicated by Ramaswamy H. SarmaHighlightsQuinoline derivatives have been designed as protease inhibitors against SARS-CoV-2.The compounds were docked at the allosteric site of SARS-CoV-2-Mpro enzyme (PDB ID: 6LU7) to study the stability of protein-ligand complex.Docking studies indicated the stable ligand-protein complexes for all designed compounds.The Toxicity Prediction by Komputer Assisted Technology protocol in DS v20.1.0.19295 software was used to evaluate the toxicity of the designed quinoline derivatives.Molecular dynamics studies indicated the formation of stable ligand-Mpro complexes.

6.
Artigo em Inglês | MEDLINE | ID: mdl-34330546

RESUMO

PURPOSE: Carbapenem inactivation method (CIM) and modified carbapenem inactivation method (mCIM) were recently developed for rapid detection of carbapenemase producing Gram negative bacilli (CP-GNB). In this study we compared the ability of modified Hodge test (MHT), CIM and mCIM to identify CP-GNB in Oman and India. METHODS: Fifty fully characterized and genotyped CP-GNB (26 OXA-48-like, 2 NDM-1 from Oman and 22 NDM-1 from India) and 8 AmpC as controls in India were subjected to MHT, CIM, mCIM and mCIM with in-house modifications. Wilcoxon paired test and receiver operating characteristics (ROC) were utilised for statistical analysis. RESULTS: Isolates were predominantly OXA-48-like genes producing Klebsiella pneumoniae from Oman and NDM-1 producing Escherichia coli from India. MHT was positive in all except one OXA-48-like producers and in 70.8 â€‹% of the NDM-1 isolates. The sensitivity of CIM in detecting 0XA-48 like and NDM-1 carbapenemases were 39.2% and 87.5% respectively. mCIM at 4 â€‹h detected 92.3 â€‹% and 79.1% of 0XA-48 and NDM-1 respectively. Using receiver operative characteristics (ROC), highest sensitivity and specificity for detection of OXA-48-like was obtained by mCIM at 4 â€‹h at cut off 17 â€‹mm while for NDM-1 CIM was the test of choice at 16 â€‹mm. CONCLUSION: CIM and mCIM are simple, cheap and easy tests to perform. CIM gave excellent results with NDM1 strains while it was quite poor in predicting OXA-48-like. We recommend CIM and eCIM for rapid identification of NDM-1 producers and mCIM at 4 â€‹h and MHT for detection of OXA-48-like. No one method can correctly detect both genotypes. As determined by ROC curves a zone of inhibition of 17 â€‹mm was considered adequate for detection of OXA-48-like and 16 â€‹mm of NDM-1 by mCIM at 4 â€‹h and CIM respectively.

7.
J Exp Bot ; 2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34185840

RESUMO

The importance of increasing photosynthetic efficiency for sustainable crop yield increases to feed the growing world population is well recognized. The natural genetic variation for leaf photosynthesis in crop plants is largely unexploited for increasing genetic yield potential. The genus Oryza, including cultivated rice and wild relatives, offers tremendous genetic variability to explore photosynthetic differences, and underlying biochemical, photochemical, and developmental bases. We quantified leaf photosynthesis and related physiological parameters for six cultivated and three wild rice genotypes, and identified photosynthetically efficient wild rice accessions. Fitting A/Ci curves and biochemical analyses showed that the leaf photosynthesis in cultivated rice varieties, IR64 and Nipponbare, was limited due to leaf nitrogen content, Rubisco activity, and electron transport rate compared to photosynthetically efficient accessions of wild rice Oryza australiensis and Oryza latifolia. The selected wild rice accessions with high leaf photosynthesis per unit area had striking anatomical features, such as larger mesophyll cells with more chloroplasts, fewer mesophyll cells between two consecutive veins, and higher mesophyll cell and chloroplast surface area exposed to intercellular space. Our results show the existence of desirable variations in Rubisco activity, electron transport rate, and leaf anatomical features in the rice system itself that could be targeted for increasing the photosynthetic efficiency of cultivated rice varieties.

8.
Dig Dis Sci ; 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33877497

RESUMO

Intestinal lymphoma, although rare, is the second most common extra-nodal site of lymphoma, following stomach. It is usually secondary to systemic involvement and is predominantly of non-Hodgkin's subtype. In addition to the risk factors for lymphomas occurring elsewhere, certain risk factors are specific for intestinal lymphoma. These include enteropathies such as celiac disease and inflammatory bowel disease. Imaging is the cornerstone in the management of intestinal lymphoma. Contrast-enhanced computed tomography or positron emission tomography-computed tomography are the preferred modalities for diagnosis, staging, monitoring response to treatment, and for follow-up evaluation. Bowel lymphomas can have various morphological patterns on imaging; however, certain characteristic features, if present, may prove invaluable in its diagnosis. Hence, it is imperative to be acquainted with the myriad of imaging findings in bowel lymphoma and its complications which may not only help in vivo distinction from other commoner bowel lesions but alter the management accordingly.

9.
eNeuro ; 8(2)2021.
Artigo em Inglês | MEDLINE | ID: mdl-33712439

RESUMO

The perception of our surrounding environment is an amalgamation of stimuli detected by sensory neurons. In Caenorhabditis elegans, olfaction is an essential behavior that determines various behavioral functions such as locomotion, feeding and development. Sensory olfactory cues also initiate downstream neuroendocrine signaling that controls aging, learning, development and reproduction. Innate sensory preferences toward odors (food, pathogens) and reproductive pheromones are modulated by 11 pairs of amphid chemosensory neurons in the head region of C. elegans Amongst these sensory neurons, the ASI neuron has neuroendocrine functions and secretes neuropeptides, insulin-like peptide (DAF-28) and the TGF-ß protein, DAF-7. Its expression levels are modulated by the presence of food (increased levels) and population density (decreased levels). A recent study has shown that EXP-1, an excitatory GABA receptor regulates DAF-7/TGF-ß levels and participates in DAF-7/TGF-ß-mediated behaviors such as aggregation and bordering. Here, we show that exp-1 mutants show defective responses toward AWC-sensed attractive odors in a non-autonomous manner through ASI neurons. Our dauer experiments reveal that in daf-7 mutants, ASI expressed EXP-1 and STR-2 (a G-protein-coupled receptor; GPCR) that partially maintained reproductive growth of animals. Further, studies suggest that neuronal connections between ASI and AWC neurons are allowed at least partially through ASI secreted DAF-7 or through alternate TGF- ß pathway/s regulated by EXP-1 and STR-2. Together, our behavioral, genetic and imaging experiments propose that EXP-1 and STR-2 integrate food cues and allow the animals to display DAF-7/TGF-ß neuroendocrine dependent or independent behavioral responses contributing to chemosensensory and developmental plasticity.


Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animais , Proteínas de Caenorhabditis elegans/genética , Mutação , Células Receptoras Sensoriais , Transdução de Sinais , Fator de Crescimento Transformador beta/genética
10.
Chemosphere ; 273: 129693, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33524742

RESUMO

Anthropogenically impacted surface waters are an important reservoir for multidrug-resistant bacteria and antibiotic-resistant genes. The present study aimed at MDR, ESBL, AmpC, efflux genes, and heavy metals resistance genes (HMRGs) in bacterial isolates from four Indian rivers belonging to different geo-climatic zones, by estimating the mode of resistance transmission exhibited by the resistant isolates. A total 71.27% isolates exhibited MDR trait, showing maximum resistance towards ß-lactams (P = 66.49%; AMX = 59.04%), lincosamides (CD = 65.96%), glycopeptides (VAN = 25.19%; TEI = 56.91%), cephalosporins (CF = 53.72%; CXM = 30.32%) sulphonamide (COT = 43.62%; TRIM = 12.77%), followed by macrolide and tetracycline. The dfrA1 and dfrB genes were detected in total 37.5% isolates whereas; dfrA1 genes were detected in 33.34%. The sul1 gene was detected in 9.76% and sul2 gene was detected in 2.44% isolates. A total of 69.40% MDR integron positive isolates were detected with intI1and intI2 detected at 89.25% and 1.07%, respectively; encoding class 1 and class 2 integron-integrase. ESBL production was confirmed in 73.13% isolates that harboured the genes blaTEM (96.84%), blaSHV (27.37%), blaOXA (13.68%) and blaCTXM (18.95%) while the frequency of HMRGs; 52.24% (zntB), 33.58% (chrA), and 6.72% (cadD). Efflux activity was confirmed in 96.26% isolates that harbored the genes acrA (93.02%), tolC (88.37%), and acrB (86.04%). AmpC (plasmid-mediated) was detected in 20.9% of the riverine isolates. Detection of such hidden molecular modes of antibiotic resistance in the rivers is alarming that requires urgent and stringent measures to control the resistance threats.


Assuntos
Antibacterianos , Integrons , Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Testes de Sensibilidade Microbiana , Plasmídeos , beta-Lactamases/genética , beta-Lactamas
11.
PLoS Genet ; 17(2): e1009346, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33524034

RESUMO

Ethanol is a widely used drug, excessive consumption of which could lead to medical conditions with diverse symptoms. Ethanol abuse causes dysfunction of memory, attention, speech and locomotion across species. Dopamine signaling plays an essential role in ethanol dependent behaviors in animals ranging from C. elegans to humans. We devised an ethanol dependent assay in which mutants in the dopamine autoreceptor, dop-2, displayed a unique sedative locomotory behavior causing the animals to move in circles while dragging the posterior half of their body. Here, we identify the posterior dopaminergic sensory neuron as being essential to modulate this behavior. We further demonstrate that in dop-2 mutants, ethanol exposure increases dopamine secretion and functions in a DVA interneuron dependent manner. DVA releases the neuropeptide NLP-12 that is known to function through cholinergic motor neurons and affect movement. Thus, DOP-2 modulates dopamine levels at the synapse and regulates alcohol induced movement through NLP-12.


Assuntos
Caenorhabditis elegans/efeitos dos fármacos , Neurônios Dopaminérgicos/efeitos dos fármacos , Etanol/farmacologia , Transmissão Sináptica/efeitos dos fármacos , Animais , Caenorhabditis elegans/genética , Caenorhabditis elegans/fisiologia , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/fisiologia , Depressores do Sistema Nervoso Central/farmacologia , Dopamina/metabolismo , Neurônios Dopaminérgicos/fisiologia , Humanos , Locomoção/efeitos dos fármacos , Neurônios Motores/efeitos dos fármacos , Neurônios Motores/fisiologia , Mutação , Neuropeptídeos/metabolismo , Receptores de Dopamina D2/genética , Receptores de Dopamina D2/fisiologia , Transdução de Sinais/efeitos dos fármacos
12.
Arch Environ Contam Toxicol ; 80(2): 499-506, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33523258

RESUMO

Infant skin is highly absorptive and sensitive to exposure from external agents (microbes, toxicants, heat, cold, etc.). Many specialized infant skincare products are currently commercially available. Although the manufacturers claim that their products are mild enough to suit the infant skin, these products need to be studied for their safety. Using animal models to examine the safety of the ever-increasing number of skincare products is not economically or logistically feasible. To overcome this problem, we suggest using a battery of microbial bioassays as a robust system for monitoring the mutagenic potential of skincare products. We picked popular infant skincare products from the Indian market and assessed them by using a battery of three microbial mutagenicity bioassays. Most of them showed significant and reproducible mutagenic potential. Our study results raise concerns about regular use of infant products and emphasize the need to enforce strict regulations for the manufacturing and safety assessment of infant products.


Assuntos
Bioensaio , Cosméticos/toxicidade , Exposição Ambiental/estatística & dados numéricos , Mutagênicos/toxicidade , Animais , Humanos , Lactente , Modelos Animais , Higiene da Pele/métodos , Testes Cutâneos
13.
J Exp Bot ; 72(12): 4355-4372, 2021 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-33587747

RESUMO

Source-sink relationships are key to overall crop performance. Detailed understanding of the factors that determine source-sink dynamics is imperative for the balance of biomass and grain yield in crop plants. We investigated the differences in source-sink relationships between a cultivated rice, Oryza sativa cv. Nipponbare, and a wild rice, Oryza australiensis, which show striking differences in biomass and grain yield. Oryza australiensis, which accumulates a higher biomass, not only showed higher photosynthesis per unit leaf area but also exported more sucrose from leaves compared with Nipponbare. However, grain features and sugar content suggested limited sucrose mobilization to grains in the wild rice due to vasculature and sucrose transporter functions. Low cell wall invertase activity and high sucrose synthase cleavage activity followed by higher expression of cellulose synthase genes in O. australiensis stem indicated that it utilized photosynthates preferentially for the synthesis of structural carbohydrates, resulting in high biomass. In contrast, source-sink relationships favored high grain yield in Nipponbare via accumulation of transitory starch in the stem, due to higher expression of starch biosynthetic genes, which is mobilized to panicles at the grain filling stage. Thus, vascular features, sucrose transport, and functions of sugar metabolic enzymes explained the differences in source-sink relationships between Nipponbare and O. australiensis.


Assuntos
Oryza , Carbono , Grão Comestível , Oryza/genética , Proteínas de Plantas/genética , Sacarose
14.
Physiol Plant ; 171(4): 620-637, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32940908

RESUMO

Abiotic stresses, including drought and salinity, negatively affect plant development and physiology at molecular and metabolic levels. Sucrose transport, mediating distribution of photosynthates in plant, is a key physiological process impacted by drought and salinity stresses, as sucrose is a prime energy and signaling molecule as well as an osmolyte. Therefore, understanding the effects of abiotic stresses on sucrose transport and transporters, and underlying genetic and molecular mechanisms, is imperative to maintain sugar homeostasis in plants under stress. Here, we investigated the effects of drought and salinity stresses on sucrose transport and distribution, and on expression levels of genes encoding Sugars Will Eventually be Exported Transporters (SWEETs), along with a potential transcription factor regulating SWEET expression in rice. We observed that drought and salinity stresses increased the sucrose content in leaf and root tissues and in phloem sap of rice indica varieties. Expression analyses of SWEET genes and histochemical analysis of ß-glucuronidase-reporter transgenic plants suggested that OsSWEET13 and OsSWEET15 are major SWEET transporters regulating the sucrose transport and levels in response to the abiotic stresses. Transactivation analyses showed that an abscisic acid (ABA)-responsive transcription factor OsbZIP72 directly binds to the promoters of OsSWEET13 and OsSWEET15 and activates their expression. Taken together, the results showed that the higher expressions of OsSWEET13 and OsSWEET15 genes, induced by binding of an ABA-responsive transcription factor OsbZIP72 to the promoters, potentially modulate sucrose transport and distribution in response to the abiotic stresses. The mechanism could possibly be targeted for maintaining sugar homeostasis in rice under drought and salinity stresses.


Assuntos
Ácido Abscísico , Oryza , Secas , Regulação da Expressão Gênica de Plantas , Oryza/genética , Oryza/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Estresse Salino , Estresse Fisiológico , Sacarose
15.
Eval Health Prof ; 44(1): 98-101, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33148018

RESUMO

A single undiagnosed COVID-19 positive patient admitted in the green zone has the potential to infect many Health Care Workers (HCWs) and other patients at any given time with resultant spread of infection and reduction in the available workforce. Despite the existing triaging strategy at the Obstetric unit of a tertiary hospital in New Delhi, where all COVID-19 suspects obstetric patients were tested and admitted in orange zone and non-suspects in green zone, asymptomatic COVID-19 positive patients were found admitted in the green zone. This was the trigger to undertake a quality improvement (QI) initiative to prevent the admission of asymptomatic COVID-19 positive patients in green zones. The QI project aimed at reducing the admission of COVID-19 positive patients in the green zone of the unit from 20% to 10% in 4 weeks' time starting 13/6/2020 by means of dynamic triaging. A COVID-19 action team was made and after an initial analysis of the problem multiple Plan-Do-Study-Act (PDSA) cycles were run to test the change ideas. The main change ideas were revised testing strategies and creating gray Zones for patients awaiting COVID-19 test results. The admission of unsuspected COVID-19 positive cases in the green zone of the unit reduced from 20% to 0% during the stipulated period. There was a significant reduction in the number of HCWs, posted in the green zone, being quarantined or test positive for COVID-19 infection as well. The authors conclude that Quality Improvement methods have the potential to develop effective strategies to prevent spread of the deadly Corona virus.


Assuntos
COVID-19/prevenção & controle , Controle de Doenças Transmissíveis/organização & administração , Obstetrícia/organização & administração , Melhoria de Qualidade/organização & administração , Triagem/organização & administração , COVID-19/diagnóstico , Humanos , Índia/epidemiologia , Programas de Rastreamento/organização & administração , SARS-CoV-2 , Centros de Atenção Terciária/organização & administração
16.
Abdom Radiol (NY) ; 46(5): 2064-2071, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33136181

RESUMO

PURPOSE: In this study, we compared non-contrast MR angiography (NC-MRA) with conventional 3D contrast-enhanced MRA (CE-MRA) in patients suspected to have renal artery stenosis (RAS). METHODS: From March 2014 to March 2020, patients who were evaluated for RAS and had a glomerular filtration rate > 30 ml/min/1.73 m2 underwent MR imaging on a 3T MR Scanner (Signa Hdxt General Electrics, Milwaukee, USA) using a Torso PA coil. The NC-MRA sequence was performed using a 3D fat-suppressed inflow inversion recovery balanced steady state free precession (SSFP) sequence (Inhance 3D Inflow IR, GE Medical) whereas the CE-MRA sequence was a 3D fast spoiled gradient echo (FSPGR). Overall quality of images was rated 1 to 4. Stenosis was reported as grade 1 (Normal), 2 (< 50% narrowing), 3 (> 50% narrowing) and 4 (Total occlusion). Grade 3 and 4 were considered haemodynamically significant. RESULTS: During the study period, 201 patients were enrolled (400 renal arteries). For hemodynamically significant (grade 3/4) stenosis, NC-MRA correctly diagnosed 72 patients (95 arteries) while in 2 patients (2 arteries), NC-MRA underdiagnosed the stenosis as grade 2 (these were found to have grade 3 stenosis on CE-MRA). The kappa value of agreement between NC-MRA and CE-MRA for detection of RAS showing excellent agreement (p < 0.001). CONCLUSION: In one of the largest series of patients so far, we found that NC-MRA is a viable alternative to CE-MRA for detection of RAS, highly correlating with CE-MRA for grade of stenosis and with additional advantage of lack of gadolinium based contrast agents toxicity.


Assuntos
Obstrução da Artéria Renal , Meios de Contraste , Humanos , Imageamento Tridimensional , Angiografia por Ressonância Magnética , Imageamento por Ressonância Magnética , Artéria Renal , Obstrução da Artéria Renal/diagnóstico por imagem , Sensibilidade e Especificidade
17.
Xenobiotica ; 51(3): 335-344, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33287643

RESUMO

Polybrominated diphenyl ethers (PBDEs) levels in environmental matrices have generally declined following their phaseout as flame retardants. The objective of this study was to determine the absorption, distribution, metabolism, and excretion of three persistent PBDEs in laying hens and their transfer into eggs. Laying hens (n = 4 per congener) received a single oral dose of BDE-99, -153, or -209 and eggs and excreta were collected daily for 7 days, then tissues were collected and analysed. Cumulative BDE-209 excretion was 93% of dose, and bioavailability was approximately 17%. Lesser amounts of BDE-99 (41%) and -153 (26%) were excreted with bioavailabilities of 87% and 79%, respectively. Phenolic metabolites were observed in excreta extracts from BDE-99 dosed birds. Cumulative transfers based on bioavailability of BDE-99, -153, and -209 to eggs were 17%, 34%, and 15%, respectively. Egg residues were primarily present in yolk (12.3%, 23.5%, and 2.1% of the total dose for BDE-99, -153, and -209, respectively). Adipose, skin, ova, intestine, and thigh muscle contained the highest levels of radioactive tissue residues. These studies demonstrate movement of PBDE residues into edible tissues and eggs of laying hens.


Assuntos
Retardadores de Chama/metabolismo , Éteres Difenil Halogenados/metabolismo , Óvulo/química , Animais , Galinhas , Feminino , Éteres Difenil Halogenados/análise
18.
Sci Total Environ ; 751: 142217, 2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-33181985

RESUMO

Global use of antibiotics has exceedingly enhanced in agricultural, veterinary and prophylactic human use in recent days. Hence, these antibiotics can easily be found in the environment. This study revealed the occurrence of emerging MDR and ESBL producing strains, pollution profile, and factors integrons (intI1 and intI2) and environmental factors associated, in the riverine systems under different ecological and geo-climatic zones were investigated. The samples were collected based on anthropogenic intervention such as discharge of domestic wastes, industrial wastes, hospital, and municipal wastes. Among 160bacterial morphotypes, 121 (75.62%) exhibited MDR trait with maximum resistance towards lincosamide (CD = 71.3%), beta-lactams (P = 70.6%; AMX = 66.3%), cephalosporin (CZ = 60.6%; CXM = 34.4%), sulfonamide (COT = 50.6%; TR = 43.8%) followed by macrolide (E = 29.4%), tetracycline (TET = 18.8%), aminoglycosides (S = 18.8%; GEN = 6.3%), fluoroquinolones (NX = 18.1%; OF = 4.4%) and carbapenem (IPM = 5.0%). IntI1 gene was detected in 73 (60.3%) of isolates, whereas intI2 was found in 11 (9.09%) isolates. Eight (6.61%) isolates carried both integron genes (intI1 and intI2). sul1 and dfrA1 genes were detected in 53 (72.6%) and 63 (86.3%) isolates, respectively. A total of 103 (85.1%) were found ESBL positive with the presence of ESBL genes in 100 (97.08%) isolates. In riverine systems most prevalent ESBL gene blaTEM (93.0%) was detected alone as well as in combination with bla genes. The data can be utilized for public awareness and regulation of guidelines by local governing bodies as an alarming threat to look-out against the prevalent resistance in environment thereby assisting in risk management during epidemics. This study is a comprehensive investigation of emerging antibiotic pollutants and its resistance in bacteria associated with factors integrons-integrase responsible for its dissemination. It may also assist in global surveillance of antibiotic resistance and policies to curtail unnecessary antibiotic use.


Assuntos
Integrases , Integrons , Antibacterianos , Humanos , Testes de Sensibilidade Microbiana , Sulfonamidas
19.
Comput Biol Chem ; 89: 107400, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33068917

RESUMO

A series of alkylated benzimidazole derivatives was synthesized and screened for their anti-HIV, anti-YFV, and broad-spectrum antiviral properties. The physicochemical parameters and drug-like properties of the compounds were assessed first, and then docking studies and MD simulations on HIV-RT allosteric sites were conducted to find the possible mode of their action. DFT analysis was also performed to confirm the nature of the hydrogen bonding interaction of active compounds. The in silico studies indicated that the molecules behaved like possible NNRTIs. The nature - polar or non-polar and position of the substituent present at fifth, sixth, and N-1 positions of the benzimidazole moiety played an important role in determining the antiviral properties of the compounds. Among the various compounds, 2-(5,6-dibromo-2-chloro-1H-benzimidazol-1-yl)ethan-1-ol (3a) showed anti-HIV activity with an appreciably low IC50 value as 0.386 × 10-5µM. Similarly, compound 2b, 3-(2-chloro-5-nitro-1H-benzimidazol-1-yl) propan-1-ol, showed excellent inhibitory property against the yellow fever virus (YFV) with EC50 value as 0.7824 × 10-2µM.


Assuntos
Benzimidazóis/farmacologia , HIV/efeitos dos fármacos , Inibidores da Transcriptase Reversa/farmacologia , Vírus da Febre Amarela/efeitos dos fármacos , Animais , Benzimidazóis/síntese química , Benzimidazóis/farmacocinética , Domínio Catalítico , Chlorocebus aethiops , Teoria da Densidade Funcional , HIV/enzimologia , Transcriptase Reversa do HIV/química , Transcriptase Reversa do HIV/metabolismo , Testes de Sensibilidade Microbiana , Modelos Químicos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Estrutura Molecular , Inibidores da Transcriptase Reversa/síntese química , Inibidores da Transcriptase Reversa/farmacocinética , Relação Estrutura-Atividade , Células Vero , Vírus da Febre Amarela/enzimologia
20.
Nitric Oxide ; 104-105: 36-43, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32891753

RESUMO

It is well established that myoglobin supports mitochondrial respiration through the storage and transport of oxygen as well as through the scavenging of nitric oxide. However, during ischemia/reperfusion (I/R), myoglobin and mitochondria both propagate myocardial injury through the production of oxidants. Nitrite, an endogenous signaling molecule and dietary constituent, mediates potent cardioprotection after I/R and this effect relies on its interaction with both myoglobin and mitochondria. While independent mechanistic studies have demonstrated that nitrite-mediated cardioprotection requires the presence of myoglobin and the post-translational S-nitrosation of critical cysteine residues on mitochondrial complex I, it is unclear whether myoglobin directly catalyzes the S-nitrosation of complex I or whether mitochondrial-dependent nitrite reductase activity contributes to S-nitrosation. Herein, using purified myoglobin and isolated mitochondria, we characterize and directly compare the nitrite reductase activities of mitochondria and myoglobin and assess their contribution to mitochondrial S-nitrosation. We demonstrate that myoglobin is a significantly more efficient nitrite reductase than isolated mitochondria. Further, deoxygenated myoglobin catalyzes the nitrite-dependent S-nitrosation of mitochondrial proteins. This reaction is enhanced in the presence of oxidized (Fe3+) myoglobin and not significantly affected by inhibitors of mitochondrial respiration. Using a Chinese Hamster Ovary cell model stably transfected with human myoglobin, we show that both myoglobin and mitochondrial complex I expression are required for nitrite-dependent attenuation of cell death after anoxia/reoxygenation. These data expand the understanding of myoglobin's role both as a nitrite reductase to a mediator of S-nitrosation and as a regulator of mitochondrial function, and have implications for nitrite-mediated cardioprotection after I/R.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...