RESUMO
The Poaceae family of plants provides cereal crops that are critical for human and animal nutrition, and also, they are an important source of biomass. Interacting plant cell wall components give rise to recalcitrance to digestion; thus, understanding the wall molecular architecture is important to improve biomass properties. Xylan is the main hemicellulose in grass cell walls. Recently, we reported structural variation in grass xylans, suggesting functional specialisation and distinct interactions with cellulose and lignin. Here, we investigated the functions of these xylans by perturbing the biosynthesis of specific xylan types. We generated CRISPR/Cas9 knockout mutants in Brachypodium distachyon XAX1 and GUX2 genes involved in xylan substitution. Using carbohydrate gel electrophoresis, we identified biochemical changes in different xylan types. Saccharification, cryo-SEM, subcritical water extraction and ssNMR were used to study wall architecture. BdXAX1A and BdGUX2 enzymes modify different types of grass xylan. Brachypodium mutant walls are likely more porous, suggesting the xylan substitutions directed by both BdXAX1A and GUX2 enzymes influence xylan-xylan and/or xylan-lignin interactions. Since xylan substitutions influence wall architecture and digestibility, our findings open new avenues to improve cereals for food and to use grass biomass for feed and the production of bioenergy and biomaterials.
Assuntos
Brachypodium , Xilanos , Animais , Humanos , Xilanos/metabolismo , Lignina/metabolismo , Brachypodium/metabolismo , Parede Celular/metabolismoRESUMO
Though uranium is usually present in its +6 oxidation state (as uranyl ion) in aqueous solutions, its conversion to oxidation states such as +4 or +5 is a challenging task. Electrochemical reduction and axial oxo activation are the preferred methods to get stable unusual oxidation states of uranium in an aqueous medium. In previous studies, dicarboxylic acid has been used to stabilize UO2+ in aqueous alkaline solutions. In the present work, a diphosphonate ligand was chosen due to its higher complexing ability compared to that of the carboxylate ligands. Neptunium complexation studies with 2,6-pyridinediphosphonic acid (PyPOH) indicated the formation of different species at different pH values and the complexation facilitates disproportionation of NpO2+ to Np4+ and NpO22+ at pH 2. Hexavalent actinides form insoluble complexes in aqueous media at pH = 2, as confirmed by UO22+ complexation studies. The in situ complexation-driven precipitation resulted in conversion to pure Np4+ in aqueous media as the Np4+-PyPOH complex. A strong complexing ability of the PyPOH ligand toward the Np4+ ion is also seen for the stabilization of the electrochemically generated U4+ in aqueous medium under aerobic conditions. The U4+-PyPOH complex was found to be stable for 3 months. Raman, UV-vis, fluorescence, and cyclic voltametric studies along with density functional theory (DFT) calculations were done to get structural insights into the PyPOH complexes of actinides in different oxidation states.
RESUMO
BACKGROUND: For any drug molecule, it is mandatory to pass the drug approval process of the concerned regulatory authority, before being marketed. The Food and Drug Administration (FDA), throughout the year, approves several new drugs for safety and efficacy. In addition to new drug approvals, FDA also works on improving access to generic drugs, aimed to lower the cost of drugs for patients and improve access to treatments. In the year 2022 twelve new drug therapies were approved for managing varying cancers. METHOD: This manuscript is focused to describe the pharmacological aspects including therapeutic uses, mechanisms of actions, pharmacokinetics, adverse effects, doses, indication for special cases, contraindications, etc., of novel FDA-approved anticancer drug therapies in the year 2022. RESULT: FDA has approved about 29% (11 out of 37) novel drug therapies for varying types of cancers such as lung cancer, breast cancer, prostate cancer, melanoma, leukemia, etc. The Center for Drug Evaluation and Research CDER has reported that 90% of these anticancer drugs (e.g. Adagrasib, Futibatinib, Mirvetuximabsoravtansine-gynx, Mosunetuzumab-axb, Nivolumab and relatlimab-rmbw, Olutasidenib, Pacritinib, Tebentafusp-tebn, Teclistamab-cqyv, and Tremelimumab-actl) as orphan drugs and recommended to treat rare or uncommon cancers such as non-small cell lung cancer, metastatic intrahepatic cholangio-carcinoma, epithelial ovarian cancer, follicular lymphoma, metastatic melanoma, metastatic uveal melanoma, etc. CDER has identified six anticancer drugs (e.g. Lutetium (177Lu)vipivotidetetraxetan, Mirvetuximabsoravtansine-gynx, Mosunetuzumab-axb, Nivolumab and relatlimab-rmbw, Tebentafusp-tebn, Teclistamab-cqyv) as first-in-class drugs i.e. drugs having different mechanisms of action from the already existing ones. The newly approved anticancer drugs shall provide more efficient treatment options for cancer patients. Three FDA-approved anticancer drugs in the year 2023 are also briefly described in the manuscript. CONCLUSION: This manuscript, describing the pharmacological aspects of eleven anticancer novel drug therapies approved by the FDA, shall serve as a helpful document for cancer patients, concerned academicians, researchers, and clinicians, especially oncologists.
RESUMO
The liquid-liquid extraction (LLE) process for lanthanide-actinide separation from the nuclear fuel cycle has several drawbacks such as, the requirement of cooling for decay heat control, the handling of large volumes of toxic volatile organic compounds (VOCs), and secondary waste generation. Alternatively reprocessing without spent fuel cooling is done by pyroprocessing, which uses high-temperature corrosive molten salts and requires elevated temperature, and is an energy-intensive process. In recent years, some of the shortcomings of both LLE and pyroprocessing are overcome by the use of room temperature ionic liquids (RTILs) as the solvents. In the present work, an attempt was made to exploit the potential of the neoteric, less-corrosive, low-VOC RTILs toward direct dissolution-based separations at ambient conditions. The present paper involves the selective dissolution of Eu2O3 in an RTIL, i.e., C4mim·NTf2 containing 2-thenoyltrifluoroacetone (HTTA) within ca. 30 min at ambient conditions; while the dissolution of AmO2 and UO2 were found to be very poor, making this an attractive method for lanthanide-actinide separation, a key step in radioactive waste management, i.e., an actinide partitioning and transmutation strategy. The quantitative dissolution of Eu2O3 from simulated spent nuclear fuel with different Eu2O3 loading was also shown. Water plays a crucial role in deciding the kinetics of dissolution and amount of the dissolved oxide. The combination of X-ray absorption, fluorescence, and UV-vis spectroscopic studies suggested the formation of the dehydrated anionic complex Ln(TTA)4- to play pivotal role in the oxide dissolution process. The structure of the complex was analyzed by density functional theory and extended X-ray absorption fine structure. The mechanism of oxide dissolution was proposed and electrochemical studies were performed to understand the possible recovery option using electrodeposition of the dissolved Eu3+.
RESUMO
INTRODUCTION: A 67-year-old female with no significant past medical history presented to the critical care department with symptoms of encephalopathy. CASE PRESENTATION: The patient's Main Concerns and the Important Clinical Findings: The patient had a history of COVID -19 vaccination (recombinant ChAdOX1 nCoV-19) 14 days prior to the symptoms. She underwent an MRI of the brain and cervical spine and a lumbar puncture. The Primary Diagnoses, Interventions, and Outcomes: The patient was examined and sent for an MRI of the brain and cervical spine, followed by extensive blood and CSF investigations to rule out any infective, paraneoplastic, connective tissue disorder, or inflammatory disorder. The patient was given steroids, and a good response was reported. The primary diagnosis was made as vaccine-induced ADEM. CONCLUSION: The clinical exam, location, sparse contrast enhancement, and CSF findings were all consistent with an acute demyelinating event, and the history of vaccination, together with the clinical situation, was found to be favourable for the development of acute disseminated encephalomyelitis.
Assuntos
COVID-19 , Encefalomielite Aguda Disseminada , Feminino , Humanos , Idoso , Encefalomielite Aguda Disseminada/induzido quimicamente , Encefalomielite Aguda Disseminada/diagnóstico por imagem , Vacinas contra COVID-19/efeitos adversos , ChAdOx1 nCoV-19 , Vacinação/efeitos adversosRESUMO
BACKGROUND AND PURPOSE: Alzheimer's disease (AD) is a degenerative neurological disorder that impairs memory, cognitive abilities, and the ability to do even most everyday activities. This neurodegenerative disease is growing increasingly common as the world's population ages. Here we reviewed some of the key findings that have shown the function of Aß peptide, oxidative stress, free radical damage Triggering Receptors Expressed on Myeloid Cells 2 (TREM2), Nitric Oxide (NO), and gut microbiota in the aetiology of AD. METHODOLOGY: The potentially relevant online medical databases, namely, PubMed, Scopus, Google Scholar, Cochrane Library, and JSTOR were exhaustively researched. In addition, the data reported in the present study were primarily intervened on the basis of the timeline selected from 1 January 2000 to 31 October 2021. The whole framework was designed substantially based on key terms and studies selected by virtue of their relevance to our investigations. RESULTS: Findings suggested that channels of free radicals, such as transition metal accumulation, and genetic factors are mainly accountable for the redox imbalance that assist to understand better the pathogenesis of AD and incorporate new therapeutic approaches. Moreover, TREM2 might elicit a protective function for microglia in AD. NO causes an increase in oxidative stress and mitochondrial damage, compromising cellular integrity and viability. The study also explored that the gut and CNS communicate with one another and that regulating gut commensal flora might be a viable therapeutic for neurodegenerative illnesses like AD. CONCLUSION: There are presently no viable therapies for Alzheimer's disease, but recent breakthroughs in our knowledge of the disease's pathophysiology may aid in the discovery of prospective therapeutic targets.
RESUMO
BackgroundPlaque reduction neutralization test (PRNT) is the gold standard to detect neutralizing capacity of the serum antibodies. Neutralizing antibody confers protection against further infection. The present study was done with the objective to measure the antibody level against SARS-CoV2 among laboratory confirmed COVID-19 cases and to evaluate whether the presence of anti-SARS-CoV2 antibodies indicate virus neutralizing capacity. MethodsOne hundred COVID-19 confirmed cases were recruited. Sociodemographic details and history of COVID-19 vaccination, contact with positive COVID-19 cases, and symptoms were ascertained using a self-developed semi-structured interview schedule. Serum samples of the participants were collected within three months from date of the positive report of COVID-19. The presence of anti-SARS-CoV-2 antibodies (IgA, IgG and IgM antibodies), receptor binding domain antibodies (anti-RBD), and neutralizing antibodies were measured. FindingsAlmost all participants had Anti-SARS-CoV2 antibodies (IgA, IgG and IgM) (99%) and Anti-RBD IgG antibodies (97%). However, only 69% had neutralizing antibodies against SARS-CoV2. Anti-RBD antibody levels were significantly higher among participants having neutralizing antibodies compared to those who didnt. InterpretationThe present study highlights that presence of antibodies against SARS-CoV2, or presence of anti-RBD antibody doesnt necessarily imply presence of neutralizing antibodies. FundingWorld Health Organisation
RESUMO
Hydrophobization of hemicellulose causes melt processing and makes them stretchable thermoplastics. Understanding how native and/or appended side chains in various hemicelluloses after chemical modification affect melt processing and material properties can help in the development of products for film packaging and substrates for stretchable electronics applications. Herein, we describe a one-step and two-step strategy for the fabrication of flexible and stretchable thermoplastics prepared by compression molding of two structurally different arabinoxylans (AX). For one-step synthesis, the n-butyl glycidyl ether epoxide ring was opened to the hydroxyl group, resulting in the introduction of alkoxide side chains. The first step in the two-step synthesis was periodate oxidation. Because the melt processability for AXs having low arabinose to xylose ratio (araf/xylp<0.5) have been limited, two structurally distinct AXs extracted from wheat bran (AXWB, araf/xylp = 3/4) and barley husk (AXBH, araf/xylp = 1/4) were used to investigate the effect of araf/xylp and hydrophobization on the melt processability and properties of the final material. Melt compression processability was achieved in AXBH derived samples. DSC and DMA confirmed that the thermoplastics derived from AXWB and AXBH had dual and single glass transition (Tg) characteristics, respectively, but the thermoplastics derived from AXBH had lower stretchability (maximum 160%) compared to the AXWB samples (maximum 300%). Higher araf/xylp values, and thus longer alkoxide side chains in AXWB-derived thermoplastics, explain the stretchability differences.
Assuntos
Hordeum , Xilanos , Biomassa , Fibras na Dieta , Hordeum/química , Xilanos/químicaRESUMO
The Omicron variant of SARS-CoV-2 is capable of infecting unvaccinated, vaccinated and previously-infected individuals due to its ability to evade neutralization by antibodies. With three sub-lineages of Omicron emerging in the last four months, there is inadequate information on the quantitative antibody response generated upon natural infection with Omicron variant and whether these antibodies offer cross-protection against other sub-lineages of Omicron variant. In this study, we characterized the growth kinetics of Kappa, Delta and Omicron variants of SARS-CoV-2 in Calu-3 cells. Relatively higher amounts infectious virus titers, cytopathic effect and disruption of epithelial barrier functions was observed with Delta variant whereas infection with Omicron variant led to a more robust induction of interferon pathway, lower level of virus replication and mild effect on epithelial barrier. The replication kinetics of BA.1 and BA.2 sub-lineages of the Omicron variant were comparable in cell culture and natural Omicron infection in a subset of individuals led to a significant increase in binding and neutralizing antibodies to both BA.1 and BA.2 sub-lineages but these levels were lower than that produced against the Delta variant. Finally, we show that Cu2+, Zn2+ and Fe2+ salts inhibited in vitro RdRp activity but only Cu2+ and Fe2+ inhibited both the Delta and Omicron variants in cell culture. Thus, our results suggest that high levels of interferons induced upon infection with Omicron variant may counter virus replication and spread. Waning neutralizing antibody titers rendered subjects susceptible to infection by Omicron variant and natural Omicron infection elicits neutralizing antibodies that can cross-react with other sub-lineages of Omicron and other variants of concern.
RESUMO
Hemicelluloses are regarded as one of the first candidates for the development of value-added materials due to their renewability, abundance, and functionality. However, because most hemicelluloses are brittle, they can only be processed as a solution and cannot be processed using industrial melt-based polymer processing techniques. In this study, arabinoxylan (AX) was hydrophobized by incorporating butyl glycidyl ether (BuGE) into the hydroxyl groups through the opening of the BuGE epoxide ring, yielding alkoxy alcohols with terminal ethers. The formed BuGE derivatives were melt processable and can be manufactured into stretchable thermoplastic films through compression molding, which has never been done before with hemicellulose modified in a single step. The structural and thermomechanical properties of the one-step synthesis approach were compared to those of a two-step synthesis with a pre-activation step to demonstrate its robustness. The strain at break for the one-step synthesized AX thermoplastic with 3 mol of BuGE is ≈200%. These findings suggest that thermoplastic polymers can be composited with hemicelluloses or that thermoplastic polymers made entirely of hemicelluloses can be designed as packaging and stretchable electronics supports.
Assuntos
Compostos de Epóxi/química , Plásticos/química , Polissacarídeos/química , Xilanos/química , Interações Hidrofóbicas e Hidrofílicas , Plásticos/síntese química , Polímeros/síntese química , Polímeros/químicaRESUMO
Understanding of how the plant cell walls of different plant species respond to pretreatment can help improve saccharification in bioconversion processes. Here, we studied the chemical and structural modifications in lignin and hemicellulose in hydrothermally pretreated poplar and wheat straw using wet chemistry and 2D heteronuclear single quantum coherence nuclear magnetic resonance (NMR) and their effects on cellulose conversion. Increased pretreatment severity reduced the levels of ßâOâ4 linkages with concomitant relatively increased levels of ßâ5 and ßâß structures in the NMR spectra. ßâ5 structures appeared at medium and high severities for wheat straw while only ßâß structures were observed at all pretreatment severities for poplar. These structural differences accounted for the differences in cellulose conversion for these biomasses at different severities. Changes in the hemicellulose component include a complete removal of arabinosyl and 4-O-methyl glucuronosyl substituents at low and medium pretreatment severities while acetyl groups were found to be relatively resistant toward hydrothermal pretreatment. This illustrates the importance of these groups, rather than xylan content, in the detrimental role of xylan in cellulose saccharification and helps explain the higher poplar recalcitrance compared to wheat straw. The results point toward the need for both enzyme preparation development and pretreatment technologies to target specific plant species.
Assuntos
Lignina/química , Espectroscopia de Ressonância Magnética , Polissacarídeos/química , Celulose/química , Celulose/metabolismo , Hidrólise , Triticum/química , Xilanos/químicaRESUMO
Developing flexible, stretchable, and thermally processable materials for packaging and stretchable electronic applications from polysaccharide-based polymers contributes to the smooth transition of the fossil-based economy to the circular bioeconomy. We present arabinoxylan (AX)-based thermoplastics obtained by ring-opening oxidation and subsequent reduction (dA-AX) combined with hydrophobization with three different glycidyl ethers [n-butyl (BuGE), isopropyl (iPrGE), and 2-ethyl hexyl (EtHGE) glycidyl ether]. We also investigate the relationship between structural composition, thermal processing, and thermomechanical properties. BuGE- and iPrGE-etherified dA-AXs showed glass-transition temperatures (Tg) far below their degradation temperatures and gave thermoplastic materials when compression-molded at 140 °C. The BuGE (3 mol)-etherified dA-AX films at 19 and 31% oxidation levels show 244% (±42) and 267% (±72) elongation, respectively. In contrast, iPrGE-dA-AX samples with shorter and branched terminals in the side chains had a maximum of 60% (±19) elongation. No studies have reported such superior elongation of AX thermoplastic films and its relationship with molar substitution and Tg. These findings have implications on the strategic development of chemical modification routes using commercial polymer processing technologies and on fine-tuning structures and properties when specific polysaccharide-based polymers are used to engineer bio-based products for film, packaging, and substrates for stretchable electronic applications.
Assuntos
Materiais Biocompatíveis/química , Compostos de Epóxi/química , Temperatura , Xilanos/química , Teste de Materiais , Estrutura Molecular , Oxirredução , Tamanho da PartículaRESUMO
BACKGROUND & OBJECTIVES: Population-based seroepidemiological studies measure the extent of SARS-CoV-2 infection in a country. We report the findings of the first round of a national serosurvey, conducted to estimate the seroprevalence of SARS-CoV-2 infection among adult population of India. METHODS: From May 11 to June 4, 2020, a randomly sampled, community-based survey was conducted in 700 villages/wards, selected from the 70 districts of the 21 States of India, categorized into four strata based on the incidence of reported COVID-19 cases. Four hundred adults per district were enrolled from 10 clusters with one adult per household. Serum samples were tested for IgG antibodies using COVID Kavach ELISA kit. All positive serum samples were re-tested using Euroimmun SARS-CoV-2 ELISA. Adjusting for survey design and serial test performance, weighted seroprevalence, number of infections, infection to case ratio (ICR) and infection fatality ratio (IFR) were calculated. Logistic regression was used to determine the factors associated with IgG positivity. RESULTS: Total of 30,283 households were visited and 28,000 individuals were enrolled. Population-weighted seroprevalence after adjusting for test performance was 0.73 per cent [95% confidence interval (CI): 0.34-1.13]. Males, living in urban slums and occupation with high risk of exposure to potentially infected persons were associated with seropositivity. A cumulative 6,468,388 adult infections (95% CI: 3,829,029-11,199,423) were estimated in India by the early May. The overall ICR was between 81.6 (95% CI: 48.3-141.4) and 130.1 (95% CI: 77.0-225.2) with May 11 and May 3, 2020 as plausible reference points for reported cases. The IFR in the surveyed districts from high stratum, where death reporting was more robust, was 11.72 (95% CI: 7.21-19.19) to 15.04 (9.26-24.62) per 10,000 adults, using May 24 and June 1, 2020 as plausible reference points for reported deaths. INTERPRETATION & CONCLUSIONS: Seroprevalence of SARS-CoV-2 was low among the adult population in India around the beginning of May 2020. Further national and local serosurveys are recommended to better inform the public health strategy for containment and mitigation of the epidemic in various parts of the country.
Assuntos
Anticorpos Antivirais/sangue , Betacoronavirus/genética , Infecções por Coronavirus/epidemiologia , Imunoglobulina G/sangue , Pneumonia Viral/epidemiologia , Adolescente , Adulto , Idoso , Betacoronavirus/patogenicidade , COVID-19 , Infecções por Coronavirus/sangue , Infecções por Coronavirus/virologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/virologia , SARS-CoV-2 , Estudos Soroepidemiológicos , Adulto JovemRESUMO
Phosphonate based ligands are well known for the extraction of 'f' block elements. Three N,O-donor N-heterocyclic aromatic diphosphonate ligands were evaluated in the present work for the extraction/separation studies of Am3+ and Eu3+. Complexation studies in aqueous medium using luminescence titration indicated the formation of anionic complexes in the case of Eu3+. Two phase liquid-liquid extraction studies were, therefore, carried out by employing Aliquat-336 as the liquid anion exchanger. The results indicated the formation of a species with a metal-ligand stoichiometry of 1 : 3 in the case of pyridine-2,6-diphosphonic acid (PyPOH). In the case of 2,2'-bipyridine-6,6'-diphosphonic acid (BipyPOH), however, a 1 : 2 complex was extracted and 1,10-phenanthroline-2,9-diphosphonic acid (PhenPOH) extracts the Am3+ and Eu3+ ions by forming both 1 : 2 and 1 : 3 complexes. Formation of these kinds of anionic complexes was further confirmed using electrospray ionization mass spectrometry (ESI-MS). DFT calculations predicted the structure of the anionic complexes. The non-selectivity of these kinds of ligands between Am3+ and Eu3+ was attributed to the presence of unfavorable covalent interactions in the metal-ligand bonds.
Assuntos
Deformidades Congênitas dos Membros/complicações , Deformidades Congênitas dos Membros/fisiopatologia , Síndrome do Abdome em Ameixa Seca/complicações , Síndrome do Abdome em Ameixa Seca/fisiopatologia , Músculos Abdominais/anormalidades , Actinas/genética , Diagnóstico Precoce , Predisposição Genética para Doença/genética , Fator 1-beta Nuclear de Hepatócito/genética , Humanos , Recém-Nascido , Deformidades Congênitas dos Membros/diagnóstico , Deformidades Congênitas dos Membros/embriologia , Masculino , Síndrome do Abdome em Ameixa Seca/diagnóstico , Síndrome do Abdome em Ameixa Seca/embriologia , Receptor Muscarínico M3RESUMO
CONTEXT: Various factors affect plasma concentrations of antitubercular drugs in different populations so dosing schedule should be adjusted after therapeutic drug monitoring. AIMS: To study variability in plasma concentrations of Rifampicin and Pyrazinamide with pre and post-meal administration of drugs in tuberculosis patients. METHODS AND MATERIAL: 52 patients of pulmonary tuberculosis, divided in to two groups, pre and post-meal through systemic randomization. After taking pre-dose sample, drugs were administered according to the group. Samples were withdrawn at 2, 4, 6, and 10h after drug administration. Analysis of samples was done using HPLC. RESULTS: Mean±1SD of Cmax of Rifampicin was 7.75±2.82µg/ml, mean±1SD of AUC0-10 was 42.17±17.25µgh/ml, adjusted Tmax was 4.25h. In pre-meal samples, the corresponding values were 7.75±2.88µg/ml, 42.83±18.47µgh/ml, 3.76h and in post-meal samples 8.03±2.30µg/ml, 41.56±16.46µgh/ml and 4.75h. Mean±1SD of Cmax levels of Pyrazinamide was 54.49±21.86µg/ml, mean±1SD of AUC0-10 was 337.94±124.28µgh/ml and adjusted Tmax was 3.49h. In pre-meal samples the corresponding values were 52.00±19.13µg/ml, 329.96±112.11µgh/ml, 3.23h, and in post-meal samples 57.43±23.61µg/ml, 345.58±136.99µgh/ml, 3.54h. CONCLUSION: There is huge variability in the plasma levels of Rifampicin and Pyrazinamide in population of this sub-himalayan region.
Assuntos
Período Pós-Prandial , Pirazinamida/farmacocinética , Rifampina/farmacocinética , Tuberculose/sangue , Adulto , Antibióticos Antituberculose/administração & dosagem , Antibióticos Antituberculose/farmacocinética , Antituberculosos/administração & dosagem , Antituberculosos/farmacocinética , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Humanos , Masculino , Pirazinamida/administração & dosagem , Rifampina/administração & dosagem , Fatores de Tempo , Tuberculose/tratamento farmacológicoRESUMO
BACKGROUND: Neeri is a well-established polyherbal formulation prescribed for renal stones by the physicians but has not been experimentally evaluated for its antiurolithiatic potential using cell-lines. OBJECTIVE: This study is aimed to scientifically substantiate the antiurolithiatic effect of Neeri extract (NRE) through calcium oxalate (CaOx) crystallization inhibition, scavenging of free radicals, and protection of renal tubular epithelial NRK-52E cells from oxalate-induced injury. MATERIALS AND METHODS: The crystallization inhibition was studied by turbidimetric assay while the free radical scavenging potential was determined for superoxide and nitric oxide (NO) radicals. The cytoprotective effect against oxalate-induced injury was assessed by estimating lactate dehydrogenase (LDH) leakage and determining cell viability using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. RESULTS: NRE significantly inhibited the CaOx crystallization in a concentration-dependent manner and also scavenged superoxide (IC50 302.88 µg/ml) and NO (IC50 300.45 µg/ml) free radicals. It did not show any significant cytotoxicity for NRK-52E cells till the highest dose (500 µg/ml) and found to be safe. When NRK-52E cells, injured by exposing to oxalate crystals for 24 h, were treated with NRE, it appreciably prevented the cell injury in a dose-dependent manner. It significantly decreased the elevated LDH leakage toward normal range and improved renal cell viability (82.37% ± 0.87%), hence, prevented growth and retention of crystals. CONCLUSION: The experimental findings concluded that Neeri is a potent antiurolithiatic formulation that inhibited CaOx crystallization and prevented tubular retention of crystals by protecting the renal cells against oxalate-induced injury as well as reducing the oxidative stress by scavenging free radicals. SUMMARY: Neeri extract significantly (P < 0.001) inhibited the in vitro crystallization (88.11% ± 7.70%) of calcium oxalateIt reduced oxidative stress by scavenging superoxide and nitric oxide free radicalsIt significantly (P < 0.001) improved the cell viability by inhibiting the leakage of lactate dehydrogenase in a dose-dependent manner. Abbreviations used: Ac: Absorbance of control, At: Absorbance of test, ANOVA: Analysis of variance, CaOx: Calcium oxalate, DMEM: Dulbecco's Modified Eagle's Medium, DMSO: Dimethyl sulfoxide, EDTA: Ethylenediaminetetraacetic acid, FBS: Fetal bovine serum, INT: Iodonitrotetrazolium, LDH: Lactate dehydrogenase, M: Molar, ml: Milliliter, mM: Millimolar, MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, NAD: Nicotinamide adenine dinucleotide, NADPH: Nicotinamide adenine dinucleotide phosphate, NBT: Nitro blue tetrazolium, nm: Nanometer, NO: Nitric oxide, NRE: Neeri extract, PMS: Phenazine methosulfate, ROS: Reactive oxygen species, Sc: Slope of the graph of control, SEM: Standard error of mean, Si: Slope of the graph with inhibitor, U/I: International unit, mg: Microgram, ml: Microliter.
RESUMO
Tuberculosis (TB) is a major public health problem, invading all age groups world-wide. It is an opportunistic infection affecting the individuals alone or with co-infections. Childhood TB is a neglected aspect and a significant health problem in epidemic areas. It constitutes more than 20% of TB incidence. Pediatric TB exists in the shadow of adult TB. The clinicians concentrate on pulmonary manifestation of TB, whereas it is a major problem in both pulmonary and extra-pulmonary infections. The rate of infection with this disease is mostly associated with poverty, social disruption and human immunodeficiency virus (HIV) infection. The diagnosis of extra-pulmonary TB (EPTB) is more difficult than pulmonary TB (PTB). Delayed diagnosis and executive treatment contribute to increase in the mortality rate in endemic areas. This article provides the evidence-based simple and safe screening method, indicating rapid, highly sensitive and specific diagnostic tests for pulmonary and EPTB in children. The most important aspect of treatment is the correct course of anti-tubercular drugs. This review serves the purpose of quick reference for microbiologists, epidemiologists, academicians, students and researchers. It provides guidance regarding early diagnosis and treatment accuracy of pediatric TB.
Assuntos
Otite Média/diagnóstico , Tuberculoma/diagnóstico , Tuberculose dos Linfonodos/diagnóstico , Tuberculose Meníngea/diagnóstico , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/epidemiologia , Tuberculose da Coluna Vertebral/diagnóstico , Tuberculose Urogenital/diagnóstico , Adulto , Criança , Pré-Escolar , Testes Diagnósticos de Rotina , Humanos , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/patogenicidade , Otite Média/microbiologia , Tuberculoma/microbiologia , Tuberculose dos Linfonodos/microbiologia , Tuberculose Meníngea/microbiologia , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/microbiologia , Tuberculose da Coluna Vertebral/microbiologia , Tuberculose Urogenital/microbiologiaRESUMO
The present study aimed to investigate the delivery potential of Etodolac (ETD) containing topical niosomal gel. Niosomal formulations were prepared by thin film hydration method at various ratios of cholesterol and Span 60 and were evaluated with respect to particle size, shape, entrapment efficiency, and in vitro characteristics. Dicetyl phosphate (DCP) was also added in the niosomal formulation. Mean particle size of niosomal formulation was found to be in the range of 2 µm to 4 µm. Niosomal formulation N2 (1 : 1) ratio of cholesterol and surfactant displayed good entrapment efficiency (96.72%). TEM analyses showed that niosomal formulation was spherical in shape. Niosomal formulation (N2) displayed high percentage of drug release after 24 h (94.91) at (1 : 1) ratio of cholesterol : surfactant. Further selected niosomal formulation was used to formulate topical gel and was characterized with respect to its various parameters such as pH, viscosity, spreadability, ex vivo study, and in vivo potential permeation. Ex vivo study showed that niosomal gel possessed better skin permeation study than the plain topical gel. Further in vivo study revealed good inhibition of inflammation in case of topical niosomal gel than plain gel and niosomal formulation. The present study suggested that topical niosomal gel formulations provide sustained and prolonged delivery of drug.
RESUMO
The present study was focused on formulating and evaluating clarithromycin (CLR) containing niosomal formulation for in vitro and in vivo pharmacokinetic behavior. Niosomal formulations (empty and drug loaded) were prepared by using different ratio of surfactant (various Span grades 20, 40, 60, and 80) and cholesterol by thin film hydration method and were evaluated for in vitro characteristics, stability studies, and in vivo study. Dicetyl phosphate (DCP) was added to the niosomal formulation. Various pharmacokinetic parameters were determined from plasma of male SD rats. Span 60 containing niosomal formulation NC2 (cholesterol to surfactant ratio 1 : 1) displayed highest entrapment efficiency with desired particle size of 4.67 µm. TEM analyses showed that niosomal formulation was spherical in shape. Niosomes containing Span 60 displayed higher percentage of drug release after 24 h as compared to other formulations. NC2 formulation was found to be stable at the end of the study on storage condition. Various pharmacokinetic parameters, namely, AUC, AUMC, and MRT of niosomal formulation, were found to be 1.5-fold, 4-fold, and 3-fold plain drug, respectively. The present study suggested that niosomal formulations provide sustained and prolonged delivery of drug with enhance bioavailability.