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1.
J Biomol Struct Dyn ; : 1-13, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34463211

RESUMO

Overcoming multi drug resistance is one of the crucial challenges to control enteric typhoid fever caused by Salmonella typhi and Salmonella paratyphi. Overexpression of efflux pumps predominantly causes drug resistance in microorganisms. Therefore, immunotherapy targeting the various efflux pumps antigens could be a promising strategy to increase the success of vaccines. An immunoinformatic approach was employed to design a Salmonellosis multi-epitope subunit vaccine peptide consisting of linear B-cell and T-cell epitopes of multidrug resistance protein families including ATP Binding Cassette (ABC), major facilitator superfamily (MFS), resistance nodulation cell division (RND), small multidrug resistance (SMR), and multidrug and toxin extrusion (MATE). The selected epitopes exhibited conservation in both S. typhi and S. paratyphi and thus could be helpful for cross-protection. Further, the final vaccine construct encompassing the peptides, adjuvants and specific linker sequences showed high immunogenicity, solubility, non-allergenic, nontoxic, and wide population coverage due to strong binding affinity to maximum HLA alleles. The three-dimensional structure was predicted, and validated using various structure validation tools. Additionally, protein-protein docking of the chimeric vaccine construct with the TLR-2 protein and molecular dynamics demonstrated stable and efficient binding. Conclusively, the immunoinformatic study showed that the novel multi epitopic vaccine construct can simulate the both T-cell and B-cell immune responses in typhoidal Salmonella serovars and could potentially be used for prophylactic or therapeutic applications.Communicated by Ramaswamy H. Sarma.

2.
J Contemp Dent Pract ; 22(3): 273-277, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34210928

RESUMO

AIM: The purpose of this study was to evaluate 2% chlorhexidine disinfectant (CHX), chitosan, and octenidine dihydrochloride (as cavity disinfectants) on microleakage in cavities restored with universal self-etch adhesive. MATERIALS AND METHODS: Eighty extracted human permanent premolars were selected. Class V cavities were prepared on the facial surface of each tooth. The teeth were then divided into four groups of 20 teeth each. For the control group after cavity preparation, no disinfectant was applied. The other 3 groups were treated with 0.1% chitosan, 2% CHX, and 0.1% octenidine dihydrochloride (OCT). All the groups were restored with universal adhesive followed by composite resin. The teeth were then immersed in 1% methylene blue dye and were sectioned buccolingually. Microleakage was checked under a stereomicroscope on both occlusal and gingival margins. RESULT: Among all the groups chitosan-treated cavities showed the least microleakage. Chlorhexidine treated cavities showed less leakage as compared to control, OCT group at both the margins. CONCLUSION: Chitosan as a cavity disinfectant improves the sealing ability of the self-etch adhesive. Furthermore, in vivo studies need to be conducted to examine the interaction and long-term effect of chitosan with the other self-etch adhesive systems. CLINICAL SIGNIFICANCE: Chitosan a natural polysaccharide can be used as a cavity disinfectant as it improves the sealing ability of self-etch adhesive.


Assuntos
Infiltração Dentária , Desinfetantes , Resinas Compostas , Preparo da Cavidade Dentária , Cimentos Dentários , Infiltração Dentária/prevenção & controle , Restauração Dentária Permanente , Adesivos Dentinários , Humanos , Cimentos de Resina
3.
J Contemp Dent Pract ; 21(1): 47-50, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32381800

RESUMO

AIMS AND OBJECTIVES: The aim of the present study was to determine the effect of different intracanal medicaments on the apical seal of BioRoot root canal sealer (RCS). MATERIALS AND METHODS: One hundred permanent single-rooted teeth were used in this study. All the samples were decoronated at the cementoenamel junction and instrumented in a sequential order from 15 to 50 number k-file. The specimens were randomly divided into five groups containing 20 teeth each. Intracanal medicaments used in this study were Metapex, triple antibiotic paste, Metrogyl DG gel forte (metronidazole gel 1.5% w/w), and curenext gel. For control group following instrumentation, the roots were obturated with laterally compacted gutta-percha with BioRoot RCS. In medicament groups after the period of 14 days, the medicaments were removed. All the four groups were obturated with BioRoot RCS and gutta-percha cones using lateral compaction technique. All the specimens were coated with nail varnish and immersed in 2% methylene blue. Then the specimens were demineralized and diphanized. The cleared teeth were analyzed by means of a stereomicroscope under 10× magnification. All the data were analyzed in SPSS version 18 software (IBM, Chicago, IL, USA). RESULT: Among all the intracanal medicaments, triple antibiotic paste showed the highest microleakage. When Metpaex and Metrogyl DG gel forte were compared with Curcuma longa, differences were not statistically significant. CONCLUSION: Among all the intracanal medicaments, triple antibiotic paste showed the highest microleakage and least was Metapex. CLINICAL SIGNIFICANCE: Incomplete removal of medicaments prevents the penetration of sealer into the dentinal tubules and interferes with the normal setting reaction, thus affecting the seal of obturating material leading to microleakage and subsequent treatment failure. Hence, while placing an intracanal medicament, it is important to consider its effect on leakage of the root canal system.


Assuntos
Infiltração Dentária , Materiais Restauradores do Canal Radicular , Hidróxido de Cálcio , Guta-Percha , Humanos , Azul de Metileno
4.
SAR QSAR Environ Res ; 30(12): 847-863, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31577156

RESUMO

Graphene oxide is most often chosen as an alternative to graphene in the applications of carbon-based nanomaterials where adsorption is the primary process. However, its adsorption properties are poorly understood. The existing reports on the adsorption mechanism of graphene oxide rely on the linear free-energy/solvation-energy relationship (LFER/LSER) models. This computational work explores the role of quantum mechanical descriptors in the adsorption of aromatic organic compounds by graphene-oxide. For this, externally predictive quantitative models based on quantum-mechanical descriptors are developed and compared with the existing LSERs for the prediction of adsorption coefficients of organic compounds at three different adsorbate concentrations. The predictivity of the models is assessed using an external prediction set of compounds not used for developing the models. Notably, the mean polarizability, but originating from the quantum mechanical exchange interactions (between electrons of parallel spin), is found to be the most significant factor in driving the adsorption on graphene oxide. The present work also proposes quantum-mechanical-LSER models based on a combination of quantum-mechanical and LSER descriptors, which are in fact found to be equally predictive as the existing LSERs. The quantum-mechanical models proposed in this work are further utilized for the prediction of adsorption coefficients of aliphatic compounds.


Assuntos
Grafite/química , Hidrocarbonetos Aromáticos/química , Modelos Químicos , Nanoestruturas/química , Adsorção , Modelos Lineares , Relação Quantitativa Estrutura-Atividade , Teoria Quântica , Reprodutibilidade dos Testes
5.
SAR QSAR Environ Res ; 30(2): 109-130, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30727761

RESUMO

Carbon nanotubes (CNTs) have taken precedence over activated carbon in various applications where adsorption is the primary process. The adsorption of chemical compounds by CNTs and activated carbon is most often predicted through linear free energy/solvation energy relationships (LFERs/LSERs). This work proposes quantum-mechanical LSER models based on a combination of quantum-mechanical descriptors and solvatochromic descriptors of LSERs for predicting the adsorption of aromatic organic compounds by activated carbon at varying adsorbate concentrations. The models are validated using state-of-the-art procedures employing an external prediction set of compounds. This work reveals the hydrogen bond donating and accepting ability of compounds to be the most influencing - but a negative - factor in the adsorption process of activated carbon. The quantum-mechanical LSERs proposed in this work are analysed and found to be equally reliable as the existing LSERs. These were further used to predict the adsorption of nucleobases, steroid hormones, agrochemicals, endocrine disruptors and pharmaceutical drugs. Notably, agrochemicals and endocrine disruptors are predicted to be adsorbed more strongly by activated carbon when compared with their adsorption by CNTs. However, quantum-mechanical LSERs predict the adsorption strength of biomolecules on activated carbon to be similar to that on the CNTs, which can be used to assess the risk associated with using carbon materials.


Assuntos
Carvão Vegetal/química , Nanotubos de Carbono/química , Compostos Orgânicos/química , Relação Quantitativa Estrutura-Atividade , Adsorção , Modelos Lineares , Modelos Químicos , Teoria Quântica
6.
J Conserv Dent ; 21(2): 153-156, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29674816

RESUMO

Introduction: The purpose of this study was to compare the incidence of dentinal crack formation after root canal preparation using ProTaper Next, OneShape, and Hyflex electrodischarge machining (HEDM). Materials and Methods: A total of 75 extracted mandibular premolars were selected. The root canals were instrumented using ProTaper Next, OneShape, and HEDM rotary files. All roots were horizontally sectioned at 3, 6, and 9 mm from apex with slow-speed saw under water cooling. The sections were observed under a stereomicroscope at ×25 to determine the absence or presence of crack. Data were analyzed using post hoc test and one-way ANOVA. Results: ProTaper Next and HEDM produced significantly less cracks than OneShape. Conclusion: Within the limitation of this in vitro study, it can be concluded that nickel-titanium instruments may cause cracks on the root surface. ProTaper Next and HEDM tend to produce less number of cracks as compared to OneShape.

7.
Indian J Otolaryngol Head Neck Surg ; 70(1): 130-136, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29456957

RESUMO

This questioner survey aimed about awareness of the Cone Beam Computed Tomography (CBCT) machine and its various clinical applications in ENT, among the ENT surgeons in the state of Odisha. 150 questioner forms on CBCT were distributed to the all the participating ENT surgeons at a state level ENT conference, out of which the response rate was 110. The participants were asked to answer 30 multiple choice questions, which were divided into 3 parts; general information on CBCT, general approach to CBCT and practice related to CBCT. The statistical analysis of the data collected was carried out by a Chi square test to compare the means at a significance level of P < 0.05. The response rate for this study was 73%. The mean age of the participant ENT surgeons was 47.9 (±19.2). Of the study population, 71.2% (89) did not ever advice CBCT in their practice. Only 33.9% (38) of the population believed that CBCT is more beneficial in the field of ENT. Only 25% (28) knew that CBCT requires lower radiation dose than conventional CT. 28.1% (31) of population believed that the spatial orientation is better in CBCT than CT. 62.5% (69) of the population did not knew that CBCT can be used in imaging sinusitis of dental origins. 75% (83) of the population did not knew that CBCT can be used in diagnosis of obstructive sleep apnoea and visualizing airway space. Only 18.8% (21) of the study population agreed that the CBCT has the potential to replace conventional CT in ENT imaging in future. In the conclusion, this study clearly showed that the number of ENT surgeons advising CBCT imaging in their practice is very less. The knowledge about various advantages and clinical applications of CBCT had been very limited. However, through continuing medical education and conducting various seminars and workshops on CBCT, imparting chapters on CBCT, in the undergraduate and post graduate curriculum will definitely help increase the awareness on CBCT among ENT fraternity.

8.
J Indian Prosthodont Soc ; 18(Suppl 2): S98, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30602883
9.
Pharmaceutics ; 9(2)2017 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-28346376

RESUMO

Carboxymethyl chitosan (CMCS) was synthesized and blended with gelatin (GE) to prepare hydrogel microspheres by w/o emulsion cross-linking in the presence of glutaraldehyde (GA), which acted as a cross-linker. 5-Fluorouracil (5-FU) was encapsulated to investigate its controlled release (CR) characteristics in acidic (pH 1.2) and alkaline (pH 7.4) buffer media. The microspheres which formed were spherical in nature, with smooth surfaces, as judged by the scanning electron microscopy (SEM). Fourier transform infrared spectroscopy (FTIR) confirmed the carboxymethylation of CS and the chemical stability of 5-FU in the formulations. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) confirmed the physical state and molecular level dispersion of 5-FU. Equilibrium swelling of microspheres was performed in water, in order to understand the water uptake properties. The in vitro release of 5-FU was extended up to 12 h in pH 7.4 phosphate buffer, revealing an encapsulation efficiency of 72%. The effects of blend composition, the extent of cross-linking, and initial drug loading on the in vitro release properties, were investigated. When analyzed through empirical equations, the release data suggested a non-Fickian transport mechanism.

10.
Pharmacogenomics J ; 17(1): 53-60, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-26667829

RESUMO

Glutathione S-transferase (GST) family is involved in a two-stage detoxification process of a wide range of environmental toxins, carcinogen and antiretroviral (ARV) therapy (ART) drugs. The aim of this study is to describe the impact of genetic polymorphisms of GSTM1, GSTT1 and GSTP1-313A/G in the risk of ARV-associated hepatotoxicity in HIV-infected individuals and its modulation in hepatotoxic patients. We enrolled a total of 34 patients with hepatotoxicity, 131 HIV-infected individuals without hepatotoxicity under non-nucleoside reverse transcriptase inhibitor containing ART and 153 unrelated healthy individuals. With a case-control design, polymorphisms of GSTM1, GSTT1 and GSTP1-313A/G gene were genotyped by PCR and restriction enzyme-length polymorphism. Genotypes of GSTT1 null were significantly higher in HIV-infected individuals as compared with healthy controls (P=0.01, odds ratio (OR)=1.54). HIV-infected individuals with GSTM1-null genotype showed higher risk (P=0.09, OR=1.37) for hepatotoxicity, but risk was not significant. On evaluating gene-gene interaction models, GSTM1 null and GSTT1 null showed significant association with the risk of hepatotoxicity in HIV-infected individuals (P=0.004, OR=2.67) owing to synergistic effect of these genes. Individuals with GSTT1-null and GSTM1-null genotypes showed higher risk of hepatotoxicity with advanced stage of (CD4<200) of HIV infection (P=0.18, OR=1.39; P=0.63, OR=1.13). In case-only analysis, GSTT1-null genotype among alcohol users showed elevated risk of hepatotoxicity in HIV-infected individuals (P=0.12, OR=1.36, 95% confidence interval (CI): 0.94-1.97) as compared with GSTT1 genotypes. The carriers GSTM1-null+GSTT1-null genotype among nevirapine user showed prominent risk of hepatotoxicity in HIV-infected individuals (P=0.12, OR=4.21, 95% CI: 0.60-29.54). Hence, we can conclude that GSTT1-null and GSTM1-null genotypes alone and in combination may predict the acquisition of hepatotoxicity.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/genética , Glutationa S-Transferase pi/genética , Glutationa Transferase/genética , Infecções por HIV/tratamento farmacológico , Variantes Farmacogenômicos , Polimorfismo de Nucleotídeo Único , Adulto , Consumo de Bebidas Alcoólicas/efeitos adversos , Estudos de Casos e Controles , Doença Hepática Induzida por Substâncias e Drogas/enzimologia , Distribuição de Qui-Quadrado , Epistasia Genética , Feminino , Interação Gene-Ambiente , Predisposição Genética para Doença , Infecções por HIV/enzimologia , Infecções por HIV/genética , Humanos , Índia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Testes Farmacogenômicos , Fenótipo , Medição de Risco , Fatores de Risco , Fumar/efeitos adversos , Resultado do Tratamento
11.
J Clin Diagn Res ; 10(10): ZC138-ZC142, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27891476

RESUMO

INTRODUCTION: Sodium hypochlorite, is the irrigant of choice for many clinicians, but its strong toxic and damaging effects on vital periapical tissues is always a matter of concern. So, the search for a root canal irrigant with a broad antimicrobial spectrum yet with a limited toxicity on vital tissues is always desirable. AIM: The study evaluated antimicrobial efficacy of Electro-Chemically Activated (ECA) water as a root canal irrigant against E. faecalis. MATERIALS AND METHODS: Forty eight single rooted human teeth were decoronated to a length of 15mm. All teeth were divided into four test groups (group A - ECA anolyte, group B - 1% sodium hypochlorite, group C - 3% sodium hypochlorite, group D - distilled water) of 12 each. Only 1ml of Ringer's solution and calibrated suspensio of E. faecalis was injected into each canal, aspirated and placed on agar plates and incubated aerobically at 37°C for two days. The suspension was aspirated and spread onto the blood agar plate and incubated. All samples were irrigated with four test solutions and Brain Heart Infusion (BHI) solution was injected into each canal then aspirated and spread onto blood agar and incubated. After inoculations Colony Forming Unit (CFU) and optical density was measured under a microscope and spectrophotometer. The data obtained were statistically analysed by one way ANOVA and Dunkan's multiple range test. RESULTS: CFU reduction was not statistically significant between the test groups. The optical density showed statistically significant difference between the test groups (p≤0.001). CONCLUSION: The antimicrobial efficacy of ECA was found to be comparable to sodium hypochlorite solutions.

12.
Phys Chem Chem Phys ; 18(25): 16730-7, 2016 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-27270616

RESUMO

The electric field experienced by a water molecule within a water cluster depends on its position relative to the rest of the water molecules. The stabilization energies and the red-shifts in the donor O-H stretching vibrations in the water clusters increase with the cluster size concomitant with the increase in the electric field experienced by the donor O-H of a particular water molecule due to the hydrogen bonding network. The red-shifts in O-H stretching frequencies show a spread of about ±100 cm(-1) against the corresponding electric fields. Deviations from linearity were marked in the region of 100-160 MV cm(-1), which can be attributed to the strain in the hydrogen bonding network, especially for structures with DDAA and DDA motifs. The linear Stark effect holds up to 200 MV cm(-1) of internal electric field for the average red-shifts in the O-H stretching frequencies, with a Stark tuning rate of 2.4 cm(-1) (MV cm(-1))(-1), suggesting the validity of the classical model in small water clusters.

14.
Indian J Dent Res ; 26(2): 210-3, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26096120

RESUMO

The temporomandibular joint is one of the most complex joints of the human body. It consists of the mandibular condyle, glenoid fossa and the articular eminence of the temporal bone. Aplasia of the condyle is usually seen as part of a syndrome otherwise it is rare. We report a case of bilateral condylar aplasia in a 20-year-old male not associated with any syndrome. The patient reported to the department with a chief complaint of the underdeveloped lower jaw. Clinical examination, conventional radiographs, and 3D computer tomography images revealed a complete absence of condyle on the right and left sides.


Assuntos
Côndilo Mandibular/anormalidades , Côndilo Mandibular/diagnóstico por imagem , Humanos , Imageamento Tridimensional , Masculino , Radiografia Panorâmica , Tomografia Computadorizada por Raios X , Adulto Jovem
15.
Int J Biol Macromol ; 75: 505-14, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25647620

RESUMO

Water-soluble acrylamide (AAm)-grafted-chitosan (CS) copolymer (AAm-g-CS) was synthesized using potassium persulfate (PPS) initiator from which interpenetrating polymer network (IPN) microspheres were prepared by water-in-oil (w/o) emulsion that are cross-linked with glutaraldehyde (GA) and used for encapsulating nifedipine (NFD). Microspheres were coated with sodium alginate (NaAlg) to enhance their pH-sensitivity for extending the release time of NFD up to 14 h, releasing with 93% of NFD. The coated and uncoated microspheres were characterized by Fourier transform infrared spectra (FTIR) and differential scanning calorimetry (DSC) to understand chemical interactions and blend compatibility. Morphology and particle size of the microspheres were assessed by scanning electron microscopy (SEM) and particle zeta analyzer, respectively. Swelling and in vitro release experiments were performed in pH 1.2 and 7.4 buffer media, which showed a dependence on IPN blend composition, extent of cross-linking and amount of AAm used. Empirical analysis of drug patterns suggested the differences between NaAlg coated and uncoated microspheres.


Assuntos
Anti-Hipertensivos/farmacologia , Microesferas , Nifedipino/farmacologia , Acrilamida/química , Varredura Diferencial de Calorimetria , Química Farmacêutica , Quitosana/química , Preparações de Ação Retardada , Glutaral/química , Concentração de Íons de Hidrogênio , Microscopia Eletrônica de Varredura , Tamanho da Partícula , Álcool de Polivinil/química , Espectroscopia de Infravermelho com Transformada de Fourier
16.
Mol Genet Metab ; 112(2): 87-122, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24667081

RESUMO

New developments in the treatment and management of phenylketonuria (PKU) as well as advances in molecular testing have emerged since the National Institutes of Health 2000 PKU Consensus Statement was released. An NIH State-of-the-Science Conference was convened in 2012 to address new findings, particularly the use of the medication sapropterin to treat some individuals with PKU, and to develop a research agenda. Prior to the 2012 conference, five working groups of experts and public members met over a 1-year period. The working groups addressed the following: long-term outcomes and management across the lifespan; PKU and pregnancy; diet control and management; pharmacologic interventions; and molecular testing, new technologies, and epidemiologic considerations. In a parallel and independent activity, an Evidence-based Practice Center supported by the Agency for Healthcare Research and Quality conducted a systematic review of adjuvant treatments for PKU; its conclusions were presented at the conference. The conference included the findings of the working groups, panel discussions from industry and international perspectives, and presentations on topics such as emerging treatments for PKU, transitioning to adult care, and the U.S. Food and Drug Administration regulatory perspective. Over 85 experts participated in the conference through information gathering and/or as presenters during the conference, and they reached several important conclusions. The most serious neurological impairments in PKU are preventable with current dietary treatment approaches. However, a variety of more subtle physical, cognitive, and behavioral consequences of even well-controlled PKU are now recognized. The best outcomes in maternal PKU occur when blood phenylalanine (Phe) concentrations are maintained between 120 and 360 µmol/L before and during pregnancy. The dietary management treatment goal for individuals with PKU is a blood Phe concentration between 120 and 360 µmol/L. The use of genotype information in the newborn period may yield valuable insights about the severity of the condition for infants diagnosed before maximal Phe levels are achieved. While emerging and established genotype-phenotype correlations may transform our understanding of PKU, establishing correlations with intellectual outcomes is more challenging. Regarding the use of sapropterin in PKU, there are significant gaps in predicting response to treatment; at least half of those with PKU will have either minimal or no response. A coordinated approach to PKU treatment improves long-term outcomes for those with PKU and facilitates the conduct of research to improve diagnosis and treatment. New drugs that are safe, efficacious, and impact a larger proportion of individuals with PKU are needed. However, it is imperative that treatment guidelines and the decision processes for determining access to treatments be tied to a solid evidence base with rigorous standards for robust and consistent data collection. The process that preceded the PKU State-of-the-Science Conference, the conference itself, and the identification of a research agenda have facilitated the development of clinical practice guidelines by professional organizations and serve as a model for other inborn errors of metabolism.


Assuntos
Biopterina/análogos & derivados , Dietoterapia , Fenilcetonúrias/sangue , Fenilcetonúrias/terapia , Guias de Prática Clínica como Assunto , Biopterina/uso terapêutico , Gerenciamento Clínico , Medicina Baseada em Evidências , Feminino , Humanos , Recém-Nascido , National Institutes of Health (U.S.) , Fenilcetonúrias/diagnóstico , Gravidez , Estados Unidos
17.
Oncogene ; 33(3): 347-57, 2014 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-23318448

RESUMO

The incidence of Barrett's esophagus (BE)-associated esophageal adenocarcinoma (EAC) is increasing. Next-generation sequencing (NGS) provides an unprecedented opportunity to uncover genomic alterations during BE pathogenesis and progression to EAC, but treatment-naive surgical specimens are scarce. The objective of this study was to establish the feasibility of using widely available endoscopic mucosal biopsies for successful NGS, using samples obtained from a BE 'progressor'. Paired-end whole-genome NGS was performed on the Illumina platform using libraries generated from mucosal biopsies of normal squamous epithelium (NSE), BE and EAC obtained from a patient who progressed to adenocarcinoma during endoscopic surveillance. Selective validation studies, including Sanger sequencing, immunohistochemistry and functional assays, were performed to confirm the NGS findings. NGS identified somatic nonsense mutations of AT-rich interactive domain 1A (SWI like) (ARID1A) and PPIE and an additional 37 missense mutations in BE and/or EAC, which were confirmed by Sanger sequencing. ARID1A mutations were detected in 15% (3/20) high-grade dysplasia (HGD)/EAC patients. Immunohistochemistry performed on an independent archival cohort demonstrated ARID1A protein loss in 0% (0/76), 4.9% (2/40), 14.3% (4/28), 16.0% (8/50) and 12.2% (12/98) of NSE, BE, low-grade dysplasia, HGD and EAC tissues, respectively, and was inversely associated with nuclear p53 accumulation (P=0.028). Enhanced cell growth, proliferation and invasion were observed on ARID1A knockdown in EAC cells. In addition, genes downstream of ARID1A that potentially contribute to the ARID1A knockdown phenotype were identified. Our studies establish the feasibility of using mucosal biopsies for NGS, which should enable the comparative analysis of larger 'progressor' versus 'non-progressor' cohorts. Further, we identify ARID1A as a novel tumor-suppressor gene in BE pathogenesis, reiterating the importance of aberrant chromatin in the metaplasia-dysplasia sequence.


Assuntos
Esôfago de Barrett/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Proteínas Nucleares/genética , Fatores de Transcrição/genética , Proteínas Supressoras de Tumor/genética , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Idoso , Esôfago de Barrett/metabolismo , Esôfago de Barrett/patologia , Biópsia , Western Blotting , Linhagem Celular Tumoral , Proliferação de Células , Proteínas de Ligação a DNA , Endoscópios , Epitélio/metabolismo , Epitélio/patologia , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Feminino , Redes Reguladoras de Genes , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Proteínas Nucleares/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Polimorfismo de Nucleotídeo Único , Interferência de RNA , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Transcrição/metabolismo , Transcriptoma , Proteínas Supressoras de Tumor/metabolismo
18.
AAPS PharmSciTech ; 13(4): 1147-57, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22956057

RESUMO

This paper reports the preparation and characterization of novel pH- and thermo-responsive blend hydrogel microspheres of sodium alginate (NaAlg) and poly(N-isopropylacrylamide)(PNIPAAm)-grafted-guar gum (GG) i.e., PNIPAAm-g-GG by emulsion cross-linking method using glutaraldehyde (GA) as a cross-linker. Isoniazid (INZ) was chosen as the model antituberculosis drug to achieve encapsulation up to 62%. INZ has a plasma half-life of 1.5 h, whose release was extended up to 12 h. Fourier transform infrared spectroscopy was used to confirm the grafting reaction and chemical stability of INZ during the encapsulation. Differential scanning calorimetry was used to investigate the drug's physical state, while powder X-ray diffraction confirmed the molecular level dispersion of INZ in the matrix. Scanning electron microscopy confirmed varying surface morphologies of the drug-loaded microspheres. Temperature- and pH-responsive nature of the blend hydrogel microspheres were investigated by equilibrium swelling, and in vitro release experiments were performed in pH 1.2 and pH 7.4 buffer media at 37°C as well as at 25°C. Kinetics of INZ release was analyzed by Ritger-Peppas empirical equation to compute the diffusional exponent parameter (n), whose value ranged between 0.27 and 0.58, indicating the release of INZ follows a diffusion swelling controlled release mechanism.


Assuntos
Acrilamidas/química , Alginatos/química , Galactanos/química , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Isoniazida/administração & dosagem , Isoniazida/química , Mananas/química , Gomas Vegetais/química , Polímeros/química , Resinas Acrílicas , Antituberculosos/administração & dosagem , Antituberculosos/química , Varredura Diferencial de Calorimetria/métodos , Química Farmacêutica/métodos , Preparações de Ação Retardada , Emulsões/química , Ácido Glucurônico/química , Glutaral/química , Meia-Vida , Ácidos Hexurônicos/química , Concentração de Íons de Hidrogênio , Cinética , Microscopia Eletrônica de Varredura/métodos , Microesferas , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Temperatura , Difração de Raios X/métodos
19.
Int J Biol Macromol ; 51(1-2): 45-55, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22560962

RESUMO

Composite blend microbeads of sodium alginate (NaAlg) with sodium carboxymethyl cellulose (NaCMC) containing magnesium aluminum silicate (MAS) particles and enteric coated with chitosan have been prepared to achieve controlled release (CR) of amoxicillin in stomach environment. The composite beads have been characterized by X-ray diffraction (XRD) to study drug distribution, DSC for understanding thermal stability and Fourier transform infrared (FTIR) spectroscopy to investigate chemical interactions as well as to assess the structure of the drug-loaded formulations. Surface morphology of the beads was investigated by scanning electron microscopy (SEM). The size distribution of beads loaded with drug as studied by particle size analyzer was in the range of 745-889 µm. The beads exhibited quite widely varying encapsulation efficiencies from 52 to 92%. Equilibrium swelling of the beads measured in water and in vitro release of amoxicillin in pH 1.2 medium suggests that drug release depends on polymer blend composition, concentration of MAS and extent of enteric coating.


Assuntos
Alginatos/química , Amoxicilina/administração & dosagem , Quitosana/química , Microesferas , Amoxicilina/química , Varredura Diferencial de Calorimetria , Química Farmacêutica , Preparações de Ação Retardada/química , Ácido Glucurônico/química , Ácidos Hexurônicos/química , Tamanho da Partícula , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
20.
Pak J Biol Sci ; 15(16): 800-3, 2012 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-24175422

RESUMO

It is known that humidity enhances the growth of mites in carpets, mattresses and other household items. The association between exposure to house dust and diseases such as asthma, chronic rhinitis and atopic dermatitis has been shown in many individuals. Large quantities of carpet dyes are used in carpet industry located in Eastern Uttar Pradesh India. Nearly 90% of the carpets are manufactured in Eastern Uttar Pradesh and remaining 10% is produced in Kashmir and other places of India. Therefore, this area is important in huge dyeing and washing industry in which nearly 760 metric tons of dyes and dye supporting chemicals as well as washing chemicals are used per year. Present study has been conducted to see the adverse health effects of carpet dye black T supra which is being greatly used in carpet industry. In the present study, Gram mixed with 20 mg kg(-1) of b.wt. day(-1) sub-lethal dose of Black T Supra carpet dye was fed to Rattus norvegicus for three months and the symptoms of dermatitis in the form of hair fall in patches on surface of body started from fifth week onward. The area of patches of hair fall increased between 6-12th weeks. In controls, such effect was not observed. In addition, a little increase in body weight, cataract in eyes and desperate walking in experimental animals were observed after fifth week of feeding Black T Supra dye. In some cases, the correlation between exposure to carpet dye black T supra and symptoms is obvious.


Assuntos
Corantes/efeitos adversos , Dermatite de Contato/etiologia , Pisos e Cobertura de Pisos , Animais , Ratos
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