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1.
Hum Mol Genet ; 29(6): 1002-1017, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-32047912

RESUMO

LgDel mice, which model the heterozygous deletion of genes at human chromosome 22q11.2 associated with DiGeorge/22q11.2 deletion syndrome (22q11DS), have cranial nerve and craniofacial dysfunction as well as disrupted suckling, feeding and swallowing, similar to key 22q11DS phenotypes. Divergent trigeminal nerve (CN V) differentiation and altered trigeminal ganglion (CNgV) cellular composition prefigure these disruptions in LgDel embryos. We therefore asked whether a distinct transcriptional state in a specific population of early differentiating LgDel cranial sensory neurons, those in CNgV, a major source of innervation for appropriate oropharyngeal function, underlies this departure from typical development. LgDel versus wild-type (WT) CNgV transcriptomes differ significantly at E10.5 just after the ganglion has coalesced. Some changes parallel altered proportions of cranial placode versus cranial neural crest-derived CNgV cells. Others are consistent with a shift in anterior-posterior patterning associated with divergent LgDel cranial nerve differentiation. The most robust quantitative distinction, however, is statistically verifiable increased variability of expression levels for most of the over 17 000 genes expressed in common in LgDel versus WT CNgV. Thus, quantitative expression changes of functionally relevant genes and increased stochastic variation across the entire CNgV transcriptome at the onset of CN V differentiation prefigure subsequent disruption of cranial nerve differentiation and oropharyngeal function in LgDel mice.


Assuntos
Síndrome de DiGeorge/patologia , Modelos Animais de Doenças , Embrião de Mamíferos/patologia , Regulação da Expressão Gênica , Células Receptoras Sensoriais/patologia , Transcriptoma , Nervo Trigêmeo/patologia , Animais , Síndrome de DiGeorge/genética , Embrião de Mamíferos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Células Receptoras Sensoriais/metabolismo , Nervo Trigêmeo/metabolismo
2.
Drug Dev Ind Pharm ; 47(6): 897-907, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34033503

RESUMO

The aim of this work was to develop self-microemulsifying lipid-based formulations of trans-resveratrol in cod liver oil, a long chain lipid, to increase its solubility, dissolution rate and oral bioavailability. Ternary phase diagrams of cod liver oil with surfactant and water as well as pseudo-ternary phase diagrams of the same by mixing cod liver oil (triglyceride) with glycerol monooleate (monoglyeride) were constructed to identify regions where microemulsions were formed. Kolliphor RH 40, Tween 80 and their 1:1-mixtures were evaluated as surfactants. No organic cosolvents were added. It was observed that cod liver oil alone did not form microemulsion with any of the surfactants used, and a 1:1 mixture of cod liver oil and glycerol monooleate was necessary to enable the formation of microemulsion. Among the surfactants, Kolliphor RH 40 provided the maximum microemulsification effect. Several formulations containing 6:4, 1:1, and 4:6 w/w ratios of lipid to surfactant using the 1:1 mixture of cod liver oil and glycerol monooleate as lipid components and Kolliphor RH 40 or its mixture with Tween 80 as surfactants were identified, and trans-resveratrol solubility in these formulations were determined. Drug concentrations used in the formulations were 80% of saturation solubility, and no organic cosolvents were used in any formulations to increase drug solubility or enable emulsification. In vitro dispersion testing in 250 mL of 0.01 N HCl (pH 2) according to the USP method 2 at 50 RPM showed that the formulations rapidly dispersed in aqueous media forming microemulsions and there was no drug precipitation.


Assuntos
Tensoativos , Água , Química Farmacêutica , Sistemas de Liberação de Medicamentos , Emulsões , Lipídeos , Tamanho da Partícula , Resveratrol , Solubilidade
3.
J Biol Chem ; 294(25): 9771-9786, 2019 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-31073026

RESUMO

The DNA damage response (DDR) is an evolutionarily conserved process essential for cell survival. Previously, we found that decreased histone expression induces mitochondrial respiration, raising the question whether the DDR also stimulates respiration. Here, using oxygen consumption and ATP assays, RT-qPCR and ChIP-qPCR methods, and dNTP analyses, we show that DDR activation in the budding yeast Saccharomyces cerevisiae, either by genetic manipulation or by growth in the presence of genotoxic chemicals, induces respiration. We observed that this induction is conferred by reduced transcription of histone genes and globally decreased DNA nucleosome occupancy. This globally altered chromatin structure increased the expression of genes encoding enzymes of tricarboxylic acid cycle, electron transport chain, oxidative phosphorylation, elevated oxygen consumption, and ATP synthesis. The elevated ATP levels resulting from DDR-stimulated respiration drove enlargement of dNTP pools; cells with a defect in respiration failed to increase dNTP synthesis and exhibited reduced fitness in the presence of DNA damage. Together, our results reveal an unexpected connection between respiration and the DDR and indicate that the benefit of increased dNTP synthesis in the face of DNA damage outweighs possible cellular damage due to increased oxygen metabolism.


Assuntos
Dano ao DNA , Nucleotídeos/metabolismo , Fosforilação Oxidativa , Consumo de Oxigênio , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/crescimento & desenvolvimento , Trifosfato de Adenosina/metabolismo , Sobrevivência Celular , Montagem e Desmontagem da Cromatina , Regulação Fúngica da Expressão Gênica , Histonas/metabolismo , Mitocôndrias/metabolismo , Saccharomyces cerevisiae/metabolismo
4.
World J Surg ; 44(8): 2511-2517, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32253465

RESUMO

INTRODUCTION: We investigated the burden of surgical conditions, level of unmet needs and reasons for non-utilization of surgical services in a slum of Ahmedabad, India. METHODS: A community-based cross-sectional study was carried out from August to December 2019. Inclusion criteria was age > 14 years; any type of injury/condition that requires surgery; subject has had surgery in last 1 year, and death information of family members. Data were stored and coded in Microsoft excel and exported to IBM SPSS statistics version 25 software for data analysis. Frequencies and proportions (categorical variable) are used to summarize utilization of surgical services and understanding surgical need. The Surgeons Overseas Assessment of Surgical was used to identify surgical met and unmet needs translated into local language. Open Data Kit software was used to install questionnaire in the "Tablet" to collect information and stress-free workflow in field. RESULTS: Out of 10,330 population in 2066 households, 7914 were more than 14 years of age. 3.46% (n = 274) people needed surgery; 116 did not avail surgery and were categorized in "unmet need." Fifty percent of individuals with surgical needs had abdominal- or extremities-related problems followed by eyes surgery need (14%); back, chest and breast surgical need was 13.5%. Seventeen percent of participants with surgical needs had wounds related to injury or accident while 63% had wounds that were not related to injury. Almost all participants had gone to a physician to seek healthcare, however 42% did not avail surgical care needed for a variety of reasons. Forty-six percent of participants needing surgical care underwent major surgical procedure, while 11% had minor procedures. Financial reasons (34.5%) and lack of trust (35.3%) were major reasons for not availing surgical care. CONCLUSIONS AND RELEVANCE: Ahmedabad is a relatively high income metropolitan city, has universally free health care and multiple healthcare facilities. Despite this, we have shown that there is significant unmet need for surgical procedures in the low-income population. A unique finding was that most patients sought a consultation but approximately 50% did not avail of the free surgical procedures under the universally free health care system in this city. We propose creation of community healthcare workers focused on surgical conditions.


Assuntos
Cirurgia Geral/estatística & dados numéricos , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Necessidades e Demandas de Serviços de Saúde , Pobreza , Adolescente , Adulto , Idoso , Estudos Transversais , Feminino , Pesquisa sobre Serviços de Saúde , Disparidades em Assistência à Saúde , Humanos , Renda , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Áreas de Pobreza , Inquéritos e Questionários , População Urbana , Adulto Jovem
5.
J Assoc Physicians India ; 68(4): 32-38, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32610844

RESUMO

MRI provides better intrinsic soft-tissue contrast with more enhanced depiction of even subtly different tissue properties making lesion evaluation easy. Faster sequences which capture arterial sequences better, lack of ionizing radiation and simultaneous evaluation of background liver parenchyma and the liver lesions are additional advantages of using MRI as the imaging technique of choice. Comprehensive liver imaging using MRI now includes T1, T2-weighted imaging and in- and opposed-phase, in addition to dynamic post-contrast imaging with proper breath holding techniques. Wider variety of liver specific contrast agents is available for use in MR imaging with the gadolinium based agents being considered the most useful and practical, particularly for lesion characterization. AIMS AND OBJECTIVES: To evaluate MRI spectrum of liver lesions in cirrhotic patients, Role of MRI in focal liver lesion evaluation and to differentiate benign versus malignant lesions. MATERIALS AND METHODS: A prospective study of OPD or IPD patients who underwent imaging tests like Ultrasonography, or CT scan for suspected chronic liver disease was done. A total 35 patients were investigated (June 2014 - November 2016) with MRI abdomen done with the patient in supine position on a Philips Achieva 3.0T MRI scanner. Standard MRI abdomen protocol, including T2W TSE in axial and coronal plane, T2W fat suppressed (SPAIR) images in axial and coronal plane, T1W TFE, in- and out-of-phase imaging and Diffusion-weighted imaging (DWI) in axial plane along with pre-contrast baseline fat-suppressed T1W imaging in at least one plane was acquired. Breath-holding was required in few sequences. 0.1 mmol/kg Gadolinium based contrast (Gadobenate) was injected at the rate of 2.5 ml/sec followed by saline flush and dynamic contrast enhanced MRI (DCE-MRI) with post-contrast fat-suppressed T1W imaging was acquired. RESULTS AND CONCLUSIONS: In cirrhosis, there is development of nodules which are initially only microscopically detectable. With progression of cirrhosis, there is development of radiologically detectable regenerative nodules, dysplastic nodules and hepatocellular carcinoma. Amongst these regenerative nodules are completely benign lesions whereas dysplastic nodules, though benign, are considered premalignant; and hepatocellular carcinoma is a malignant condition. Differentiation of benign versus malignant lesions is possible on the basis of enhancement pattern in dynamic contrast enhanced MRI. The signal characteristics of focal lesions and other findings like portal vein thrombosis are helpful, give additional clue to the diagnosis and also helpful in assigning LIRADS grade to a lesion. Also, MRI characterization after gadolinium based contrast injection was found to be similar to the previous imaging based on non-gadolinium contrast agents.


Assuntos
Carcinoma Hepatocelular , Cirrose Hepática , Neoplasias Hepáticas , Meios de Contraste , Humanos , Imageamento por Ressonância Magnética , Estudos Prospectivos , Sensibilidade e Especificidade
6.
Pol J Radiol ; 85: e144-e154, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32322321

RESUMO

PURPOSE: Pulmonary tuberculosis (PTB) has clinically significant sequelae, even after recommended treatment completion. It is important to recognise these sequelae for accurate assessment of severity and treatment planning, if indicated. MATERIAL AND METHODS: We retrospectively analysed contrast-enhanced computed tomography (CT) scans of chest of 100 patients with previous history of treated pulmonary tuberculosis, excluding those with active pulmonary disease. CT findings were analysed based on parenchymal, airway, pleural, mediastinal, and vascular sequelae of PTB. RESULTS: Parenchymal sequelae included fibrosis with architectural distortion and volume loss (90%), cavities (21%) (with aspergillomas noted in 19% of these cases), and tuberculomas (54%). Airway involvement was noted as bronchiectasis (77%) and bronchial stenosis (4%) but none with broncholithiasis. Mediastinal sequelae included lymph node calcification (74%), fibrosing mediastinitis (1%), and pericardial tuberculosis (2%). Pleural sequelae included pleural thickening (22%), with 40.9% of these patients showing calcifications, and one patient with chronic chylous pleural effusion. Vascular sequelae included Rasmussen aneurysms (4%), enlarged bronchial arteries (3%), and systemic bronchial collaterals in 1% of our patients. CONCLUSIONS: PTB has multiple appalling sequelae, which require due attention and appropriate treatment in symptomatic cases. Radiological evaluation forms an integral part in patient assessment and decision making.

7.
Dev Biol ; 425(1): 85-99, 2017 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-28315296

RESUMO

Cranial sensory ganglia are components of the peripheral nervous system that possess a significant somatosensory role and include neurons within the trigeminal and epibranchial nerve bundles. Although it is well established that these ganglia arise from interactions between neural crest and neurogenic placode cells, the molecular basis of ganglia assembly is still poorly understood. Members of the Annexin protein superfamily play key roles in sensory nervous system development throughout metazoans. Annexin A6 is expressed in chick trigeminal and epibranchial placode cell-derived neuroblasts and neurons, but its function in cranial ganglia formation has not been elucidated. To this end, we interrogated the role of Annexin A6 using gene perturbation studies in the chick embryo. Our data reveal that placode cell-derived neuroblasts with reduced Annexin A6 levels ingress and migrate normally to the ganglionic anlage, where neural crest cell corridors correctly form around them. Strikingly, while Annexin A6-depleted placode cell-derived neurons still express mature neuronal markers, they fail to form two long processes, which are considered morphological features of mature neurons, and no longer innervate their designated targets due to the absence of this bipolar morphology. Moreover, overexpression of Annexin A6 causes some placode cell-derived neurons to form extra protrusions alongside these bipolar processes. These data demonstrate that the molecular program associated with neuronal maturation is distinct from that orchestrating changes in neuronal morphology, and, importantly, reveal Annexin A6 to be a key membrane scaffolding protein during sensory neuron membrane biogenesis. Collectively, our results provide novel insight into mechanisms underscoring morphological changes within placode cell-derived neurons that are essential for cranial gangliogenesis.


Assuntos
Anexina A6/metabolismo , Proteínas Aviárias/metabolismo , Membrana Celular/metabolismo , Gânglios Sensitivos/metabolismo , Células Receptoras Sensoriais/metabolismo , Crânio/inervação , Processamento Alternativo , Animais , Anexina A6/genética , Proteínas Aviárias/genética , Sequência de Bases , Embrião de Galinha , Galinhas , Gânglios Sensitivos/citologia , Gânglios Sensitivos/embriologia , Regulação da Expressão Gênica no Desenvolvimento , Técnicas de Silenciamento de Genes , Immunoblotting , Microscopia Confocal , Células-Tronco Neurais/citologia , Células-Tronco Neurais/metabolismo , Células Receptoras Sensoriais/citologia , Homologia de Sequência do Ácido Nucleico
8.
Drug Chem Toxicol ; 41(3): 259-269, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29072510

RESUMO

Several studies documented the ameliorative effects of curcumin which plays a pivotal role in radical scavenging activities. It also participates in various cellular pathways and interacts with multiple targets. In the present study, we investigated the ameliorative effect of curcumin upon chromosomal genotoxicity induced by cyclosporine, an immunosuppressant, using in vitro approaches. A plausible mechanism of how curcumin mitigates the genotoxic implications of cyclosporine was ascertained using in silico tools. We observed that the curcumin reduces the genotoxic consequences made by cyclosporine upon cell cycle checkpoints and associated chromosomal/DNA manifestations. In addition, we presented the mechanistic details of curcumin interaction with various biomacromolecule types using docking experiments which showed that the possible radical scavenging activities can only be emerged by inducing the expression of antioxidant enzymes, supported by available experimental evidences. We anticipate that the induction of antioxidant enzymes by curcumin would activate Nrf2-Keap1 pathway as the plausible mechanism to exert anti-inflammatory response as demonstrated in renal epithelial cells.


Assuntos
Curcumina/farmacologia , Ciclosporina/toxicidade , Adulto , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Dano ao DNA , Indução Enzimática/efeitos dos fármacos , Humanos , Testes para Micronúcleos , Troca de Cromátide Irmã/efeitos dos fármacos
9.
Drug Dev Ind Pharm ; 44(2): 215-223, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29057677

RESUMO

The primary objective of this study was to develop lipid-based self-microemulsifying drug delivery systems (SMEDDS) without using any organic cosolvents that would spontaneously form microemulsions upon dilution with water. Cosolvents were avoided to prevent possible precipitation of drug upon dilution and other stability issues. Different polysorbates, namely, Tween 20, Tween 40, Tween 60, and Tween 80, were used as surfactants, and Captex 355 EP/NF (glycerol tricaprylate/caprate) or its 1:1 mixture with Capmul MCM NF (glycerol monocaprylocaprate) were used as lipids. Captex 355-Tween-water ternary phase diagrams showed that oil-in-water microemulsions were formed only when the surfactant content was high (80-90%) and the lipid content low (10-20%). Thus, mixtures of Tweens with Captex 355 alone were not suitable to prepare SMEDDS with substantial lipid contents. However, when Captex 355 was replaced with the 1:1 mixture of Captex 355 and Capmul MCM, clear isotropic microemulsion regions in phase diagrams with sizes in the increasing order of Tween 20 < Tween 40 < Tween 60 < Tween 80 were obtained. Tween 80 had the most profound effect among all surfactants as microemulsions were formed with lipid to surfactant ratios as high as 7:3, which may be attributed to the presence of double bond in its side chain that increased the curvature of surfactant layer. Thus, lipid-surfactant mixtures containing 1:1 mixture of medium chain triglyceride (Captex 355) and monoglyceride (Capmul MCM) and as low as 30% Tween 80 were identified as organic cosolvent-free systems for the preparation of SMEDDS. Formulations with a model drug, probucol, dispersed spontaneously and rapidly upon dilution with water to form microemulsions without any drug precipitation.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Emulsões/química , Polissorbatos/química , Probucol/administração & dosagem , Caprilatos/química , Química Farmacêutica , Cromatografia Líquida de Alta Pressão , Diglicerídeos/química , Liberação Controlada de Fármacos , Monoglicerídeos/química , Tamanho da Partícula , Probucol/química , Tensoativos/química , Triglicerídeos/química
10.
Drug Dev Ind Pharm ; 44(6): 895-901, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29254385

RESUMO

The objective of the study was to develop a self-microemulsifying drug delivery system (SMEDDS), also known as microemulsion preconcentrate, for oral delivery of five poorly water-soluble nutraceuticals or bioactive agents, namely, vitamin A, vitamin K2, coenzyme Q10, quercetin and trans-resveratrol. The SMEDDS contained a 1:1 mixture (w/w) of Capmul MCM NF (a medium chain monoglyceride) and Captex 355 EP/NF (a medium chain triglyceride) as the hydrophobic lipid and Tween 80 (polysorbate 80) as the hydrophilic surfactant. The lipid and surfactant were mixed at 50:50 w/w ratio. All three of the SMEDDS components have GRAS or safe food additive status. The solubility of nutraceuticals was determined in Capmul MCM, Captex 355, Tween 80, and the SMEDDS (microemulsion preconcentrate mixture). The solubility values of vitamin A palmitate, vitamin K2, coenzyme Q10, quercetin, and trans-resveratrol per g of SMEDDS were, respectively, 500, 12, 8, 56, and 87 mg. Appropriate formulations of nutraceuticals were prepared and filled into hard gelatin capsules. They were then subjected to in vitro dispersion testing using 250 mL of 0.01 N HCl in USP dissolution apparatus II. The dispersion test showed that all SMEDDS containing nutraceuticals dispersed spontaneously to form microemulsions after disintegration of capsule shells with globule size in the range of 25 to 200 nm. From all formulations, except that of vitamin K2, >80-90% nutraceuticals dispersed in 5-10 min and there was no precipitation of compounds during the test period of 120 min. Some variation in dispersion of vitamin K2 was observed due to the nature of the material used (vitamin K2 pre-adsorbed onto calcium phosphate). The present report provides a simple and organic cosolvent-free lipid-based SMEDDS for the oral delivery of poorly water-soluble nutraceuticals. Although a 50:50 w/w mixture of lipid to surfactant was used, the lipid content may be increased to 70:30 without compromising the formation of microemulsion.


Assuntos
Suplementos Nutricionais/normas , Diglicerídeos/administração & dosagem , Glicerídeos/química , Lipídeos/química , Monoglicerídeos/administração & dosagem , Polissorbatos/química , Tensoativos/química , Triglicerídeos/química , Diglicerídeos/química , Composição de Medicamentos , Sistemas de Liberação de Medicamentos , Monoglicerídeos/química , Polissorbatos/administração & dosagem , Solubilidade , Água
12.
Indian J Exp Biol ; 54(8): 502-8, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-28577517

RESUMO

Lead (Pb) which plays a significant role in modern industry is related to a broad range of physiological, biochemical, behavioural and genetical dysfunctions. Its exposure leads to an increased frequency of genetic aberrations in humans. Hence, this study was designed to assess the genotoxic effect of lead acetate at three dosage levels (10, 25 and 50 µg/mL) by employing: the Cytokinesis Block Micronucleus (CBMN) assay and the Comet assay in Peripheral Blood Lymphocyte Cultures. The results of this study revealed an increased level of DNA damage among treated groups. A significant increase in the tail length of comets and other indices was observed at 25 and 50 µg/mL concentrations comparatively. Thus, lead acetate induced single-strand breaks (SSB) and double strand breaks (DSB) in DNA, alkali-labile sites (ALS), oxidative DNA damage as well as DNA-DNA/DNA-protein/DNA-metal cross linking as evidenced by the Comet assay. The chromosome breakage, DNA misrepair, chromosome loss and telomere end fusion were determined by the Micronucleus assay. Micronucleus frequency in treated lymphocytes was significantly higher as compared to controls. Nucleoplasmic bridges increased significantly and Nuclear buds increased at higher two doses only in exposed cultures. Thus, these assays are better indices for lead induced genotoxicity and metal-nucleus interactions.


Assuntos
Ensaio Cometa , Quebras de DNA de Cadeia Dupla , Quebras de DNA de Cadeia Simples , Linfócitos/efeitos dos fármacos , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Testes para Micronúcleos , Mutagênicos/toxicidade , Compostos Organometálicos/toxicidade , Adulto , Células Cultivadas , Relação Dose-Resposta a Droga , Humanos , Linfócitos/patologia , Pessoa de Meia-Idade , Estresse Oxidativo/efeitos dos fármacos
14.
Glob Ment Health (Camb) ; 11: e20, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38572256

RESUMO

Measurement-based peer supervision is one strategy to assure the quality of psychological treatments delivered by non-mental health specialist providers. In this formative study, we aimed to 1) describe the development and 2) examine the acceptability and feasibility of PEERS (Promoting Effective mental healthcare through peER Supervision)-a novel smartphone app that aims to facilitate registering and scheduling patients, collecting patient outcomes, rating therapy quality and assessing supervision quality-among frontline treatment providers delivering behavioral activation treatment for depression. The PEERS prototype was developed and tested in 2021, and version 1 was launched in 2022. To date, 215 treatment providers (98% female; ages 30-35) in Madhya Pradesh and Goa, India, have been trained to use PEERS and 65.58% have completed the supplemental, virtual PEERS course. Focus group discussions with 98 providers were examined according to four themes-training and education, app effectiveness, user experience and adherence and data privacy and safety. This yielded commonly endorsed facilitators (e.g., collaborative learning through group supervision, the convenience of consolidated patient data), barriers (e.g., difficulties with new technologies) and suggested changes (e.g., esthetic improvements, suicide risk assessment prompt). The PEERS app has the potential to scale measurement-based peer supervision to facilitate quality assurance of psychological treatments across contexts.

15.
Pharm Res ; 29(10): 2817-32, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22371051

RESUMO

PURPOSE: To develop solid self-emulsifying drug delivery systems (SEDDS) for lipids using poloxamer 188 as both solidifying and emulsifying agents. METHODS: Mixtures of various lipids with poloxamer 188 and PEG 8000 were prepared at ~75°C. The molten mixtures, with and without dissolved drugs (fenofibrate and probucol), were then cooled to room temperature. When solids formed, they were characterized by powder XRD, DSC, microscopy using cross-polarization and confocal fluorescence techniques, dispersion test in water and particle size analysis of dispersions. RESULTS: When mixed with poloxamer 188 or PEG 8000, lipids consisting of monoesters of fatty acids with glycerol or propylene glycol formed solid systems, but not di- and tri-esters, which showed phase separation. Added to water, the solid systems containing poloxamer 188 started to disperse in water forming oil globules of 200-600 nm. No emulsification of lipids was observed from solids containing PEG 8000, indicating that the surfactant property of poloxamer 188 was responsible for emulsification. Powder XRD, DSC and microscopic examination revealed that poloxamer 188 and PEG 8000 maintained their crystallinity in solid systems, while the lipids were interspersed in between crystalline regions. The drug remained solubilized in the lipid phase. CONCLUSIONS: A novel solid SEDDS is developed where the drug can be solubilized in liquid lipids and then the lipidic solution can be converted to solid mass by dispersing into the microstructure of poloxamer 188.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Emulsificantes/química , Emulsões/química , Ácidos Graxos/química , Fenofibrato/química , Poloxâmero/química , Probucol/química , Glicerol/química , Tamanho da Partícula , Polietilenoglicóis/química , Solubilidade , Água/química
16.
Proc Natl Acad Sci U S A ; 106(38): 16399-404, 2009 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-19805311

RESUMO

Bacteria have a complex internal organization with specific localization of many proteins and DNA, which dynamically move during the cell cycle and in response to changing environmental stimuli. Much less is known, however, about the localization and movements of RNA molecules. By modifying our previous RNA labeling system, we monitor the expression and localization of a model RNA transcript in live Escherichia coli cells. Our results reveal that the target RNA is not evenly distributed within the cell and localizes laterally along the long cell axis, in a pattern suggesting the existence of ordered helical RNA structures reminiscent of known bacterial cytoskeletal cellular elements.


Assuntos
Escherichia coli/metabolismo , Proteínas de Fluorescência Verde/metabolismo , RNA Bacteriano/metabolismo , Transcrição Gênica , Escherichia coli/citologia , Escherichia coli/genética , Fator de Iniciação 4A em Eucariotos/genética , Fator de Iniciação 4A em Eucariotos/metabolismo , Regulação Bacteriana da Expressão Gênica , Proteínas de Fluorescência Verde/genética , Cinética , Microscopia de Fluorescência , RNA Bacteriano/genética , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Fatores de Tempo
17.
Cureus ; 14(4): e23898, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35530866

RESUMO

The consideration of regional analgesia (RA) in below-knee surgeries is always a controversial topic due to the fear of masking symptoms of developing compartment syndrome (CS) in the postoperative period. Compartment syndrome (CS) has been found frequently in below-knee surgeries, particularly among tibial diaphyseal fractures. Like any other surgery, below-knee surgeries have significant postoperative pain that requires effective postoperative analgesia protocol. The analgesia quality makes a big difference when compared with or without RA. Also, the presence or absence of RA cannot prevent or promote the development of CS. Therefore, patients should not be deprived of their right to remain pain-free in the postoperative period by compromising the analgesia protocol. The pain out of proportion to the surgery or injury is a typical symptom of developing CS, which can cause increased analgesic demands postoperatively. Timely diagnosis and treatment of CS require vigilant postoperative monitoring of the warning signs by trained staff. Avoiding RA for fear of presumed masking of symptoms and delaying CS diagnosis may not be a solution instead of choosing an appropriate RA with regular postoperative monitoring for such warning symptoms. The high-volume proximal adductor canal (Hi-PAC) block has been described as a procedure-specific and motor-sparing RA technique appropriate for below-knee surgeries. In this prospective study, we evaluated the analgesic efficacy of the Hi-PAC block in below-knee surgeries. We also observed the effect of the Hi-PAC block, due to proximal and distal drug distribution, on masking the symptoms of the developing CS during postoperative monitoring. We found the Hi-PAC block to be a safer and more effective RA alternative for below-knee surgeries with an added motor-sparing benefit that facilitated early mobility and discharge. Its property of not interfering with postoperative surveillance to detect the symptoms of CS and intervene in time helps deal with the anxiety of CS in below-knee surgeries.

18.
Cureus ; 14(2): e22530, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35345738

RESUMO

Background There is a theory-praxis gap related to health literacy interventions focused on non-communicable diseases (NCDs) among young people. We designed an NCD curriculum and investigated its' effect on health literacy in non-medical, non-nursing college students in India. We deliberately selected non-medical and non-nursing college students (age 17 to 22 years) as we hypothesized, they would have a minimum baseline knowledge of NCDs. Methods We initially carried out a pilot study on 85 students in a four-day-long workshop (32 teaching hours) using empirically developed health literacy instrument. We administered the curriculum to 120 randomly selected students in four colleges, while 50 students were assigned to the comparison group. The curriculum was given over four days for a total of 32 hours. Approval was sought to give four credits for completion of the course. Each lecture comprised didactics, followed by discussion, and skills testing of measuring blood pressure and blood sugar. Health literacy was measured using a specifically designed tool at baseline and endline. The difference in health literacy scores between the two time-points (timepoint 1: before delivering the curriculum, time-point 2: at the end of four days of training) was analyzed using the t-test. Multiple linear and Poisson regression models were used to account for covariates. Results The average difference between the intervention and the control group in baseline scores was 0.05% points (unpaired t-test statistics: -1.36, degrees of freedom 103.15, p>0.05). The same at endline was 20.59% points (unpaired t-test statistics: -11.31, degrees of freedom 138.14, p<0.001). The endline to baseline difference in health literacy scores was 18.54% points higher in the intervention group versus the control group (unpaired t-test statistics: -10.88, degrees of freedom 161.32, p<0.001). The difference-in-difference scores remained significant after accounting for college setting and baseline score (Multivariable linear regression model, ß: 19.62% points, p<0.001). None of the socio-economic characteristics were significantly associated with the difference in the difference scores, independent of the intervention effect. The proportion of participants scoring 40% or above on the health literacy measure at endline was significantly higher in the intervention versus the control group (p<0.001). Conclusions We provide empirical data to support the incorporation of NCDs as a credit course in college curricula in low- and middle-income countries. Our findings showed that a theory-driven skills-focused curriculum may be a tool for enhancing NCD health literacy in Indian youth from diverse academic and socio-economic backgrounds.

19.
Indian J Radiol Imaging ; 32(2): 266-269, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35924131

RESUMO

Introduction The anterior choroidal artery is a branch of the terminal internal carotid artery (ICA) that is often an incidentally detected anomaly. The hyperplastic variant has been linked with an increased risk of aneurysms. We explore the role of magnetic resonance (MR) angiography in the detection of this variant and its impact of presentation of patients. Patient Presentation A 62-year-old diabetic and hypertensive male came to the casualty with complaints of giddiness, left-sided weakness, and loss of coordination for the last 2 to 3 days. He was provisionally diagnosed with a posterior circulation stroke. Management and Outcome Magnetic resonance imaging of brain revealed an acute infarct in the right thalamus and the midbrain. Time-of-flight angiography sequences were done that showed hypoplasia of the A1 segment of the left anterior cerebral artery, fetal origin of the right posterior cerebral artery, narrowing of the left ICA, and a hyperplastic left anterior choroidal artery. He was managed conservatively with antiplatelets. He later underwent a digital subtraction angiography that revealed significant narrowing of the left ICA for which he was advised carotid stenting. However, the patient was unwilling for the procedure and was discharged on oral medication with stable vitals. Conclusion Anatomical variations in the intracranial vasculature impact ischemia territory and the approach to intracranial pathology. Hyperplastic anterior choroidal artery results from the abnormal persistence of fetal pattern of vascular supply. It is important to recognize the presence of a hyperplastic anterior choroidal artery as it impacts both disease presentation and management of these patients. MR angiography allows for noninvasive and reliable detection of these anomalies in patients without the risks associated with radiation or contrast exposure in conventional/computed tomography angiography.

20.
J Chem Eng Data ; 56(11): 4126-4132, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22096257

RESUMO

For the HEPPS buffer under investigation, there are seven buffer solutions without NaCl and eight buffer solutions that contain Cl(-) and have an ionic strength (I = 0.16 mol·kg(-1)), which is similar to that of blood plasma. These buffer solutions have been evaluated in the temperature range of (278.15 to 328.15) K using the extended Debye- Hückel equation and the Bates-Guggenheim convention. The previously determined E(j) values have been used to determine the operational pH values of HEPPS buffer solutions at (298.15 and 310.15) K. These are recommended as secondary standard reference solutions for pH measurements in saline media with an isotonic ionic strength of I = 0.16 mol·kg(-1).

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