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1.
J Clin Neurosci ; 120: 30-35, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38176112

RESUMO

Intraoperative bleeding poses a substantial challenge, particularly in neuro-spine surgeries leading to complications such as hematomas, infections, and hemodynamic instability. Despite their proven efficacy, use of topical hemostatic agents (THAs) lacks comprehensive published literature and guidelines particularly in the Indian setting. The present study provides the first-ever Indian expert panel recommendations for effective adjunct THA use in different intraoperative bleeding sites and situations in neuro-spine surgeries. A comprehensive approach, encompassing a literature review, followed by experience sharing in a meeting using a survey helped integrate expert opinions in the form of practical algorithms to guide THA selection. Our survey results revealed a strong inclination towards specific THAs, flowable gelatin + thrombin being choice of THA for difficult to access and problematic bleeding situations during tumor removal/resection, transsphenoidal hypophysectomy and skull-based procedures. Both oxidized regenerated cellulose (ORC)/Fibrillar and flowable gelatin + thrombin were recommended for continuous oozing. ORC/Fibrillar was preferred for arteriovenous and cavernous malformations. This expert-panel guidance on THA use aims to optimize hemostat use practices and improve surgical outcomes in neuro-spine surgery.


Assuntos
Hemostáticos , Humanos , Hemostáticos/uso terapêutico , Trombina/uso terapêutico , Gelatina , Hemostasia Cirúrgica , Perda Sanguínea Cirúrgica/prevenção & controle
2.
Acta Neurochir Suppl ; 135: 53-59, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38153449

RESUMO

AIM: Cerebellar mutism syndrome (CMS) is a morbid complication of posterior fossa surgery in children. This review focuses on the current understanding of pathophysiology in the white matter tracts (WMT) using diffusion tensor imaging (DTI). MATERIAL AND METHODS: A series of 38 patients operated on for posterior fossa tumors in our institute between December 2019 till May 2021 were evaluated neurologically along with characteristics of mutism and DTI imaging (fractional anisotropy) in preoperative and postoperative periods. We also noted tumor size, location, volume, brainstem compression, cerebellar peduncle involvement, extent of resection, surgical approach, and histopathology. RESULT: Cerebellar mutism developed in five patients. The mean age, male sex, tumor size >5 cm, superior cerebellar peduncle involvement, and vermian incision were found to have positive correlation with the development of CMS. They showed reduction in fractional anisotropy in superior cerebellar peduncle (SCP) following resection; however, others' WMT did not show any significant change in fractional anisotropy values pre- or post-surgery. CONCLUSION: Our study suggests that functional disruption of WMT, i.e., superior cerebellar peduncle and dentato-thalamo-cortical tract (DTC) is the underlying pathophysiological component of CMS. Taking this into consideration, we need to deploy techniques to limit the damage to the superior cerebellar peduncle and DTC using neurophysiological monitoring.


Assuntos
Neoplasias Encefálicas , Neoplasias Infratentoriais , Mutismo , Criança , Humanos , Masculino , Imagem de Tensor de Difusão , Mutismo/diagnóstico por imagem , Mutismo/etiologia , Neoplasias Infratentoriais/diagnóstico por imagem , Neoplasias Infratentoriais/cirurgia , Prognóstico , Síndrome
3.
AAPS PharmSciTech ; 24(6): 154, 2023 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-37466741

RESUMO

The aim of the study was to develop and optimise drug-in-adhesive (DIA) transdermal patch of duloxetine HCl for enhanced drug delivery. DIA patch so developed reduced the dose and dosing frequency by enhancing bio-performance of the drug. A transdermal DIA patch having Duro-Tak 87-2287 as DIA polymer and Transcutol P as permeation enhancer loaded with 40% drug previously complexed with MeßCD duly characterised (FTIR, DSC, and SEM) was developed for in vivo study. Pharmacokinetic parameters of developed formulation were assessed and compared with oral route of administration. Among various permeation enhancers (PEs), Transcutol P exhibited most enhanced permeation (ER ≈ 1.99) in terms of flux and Q24 compared to control group having. Mean of maximum plasma concentration (Cmax) and area under time-concentration curve (AUC0-72) in Wistar rats (n = 6) for transdermal patch (10 mg/kg) was found to be 70.31 ± 11.2 ng/ml and 2997.29 ± 387.4 ng/ml*h, respectively, and were considerably higher than oral dose of DLX (20 mg/kg and 10 mg/kg). Albeit, T1/2 was higher in case of transdermal delivery, but this was due to sustained behaviour of delivery system. These findings highlight the significance of both inclusion complexation and transdermal delivery of DLX using DIA patch for efficient drug absorption.


Assuntos
Adesivos , Absorção Cutânea , Ratos , Animais , Cloridrato de Duloxetina , Ratos Wistar , Administração Cutânea , Adesivos/metabolismo , Adesivo Transdérmico , Pele/metabolismo
4.
Neurochem Res ; 48(10): 3055-3072, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37329447

RESUMO

There is an unmet need to develop alternative therapeutic strategies to not only restrain seizures but also to alleviate the underlying pathologies and sequelae. Berberine (BBR), an isoquinoline alkaloid, has shown promising effect in the kindling model of epileptogenesis, but due to the poor oral bioavailability its clinical application is limited. So, the present study was designed to study the neuroprotective effect of BBR nanoparticles (enhanced bioavailability as compared to BBR) against seizures in pentylenetetrazole (PTZ) induced kindling model of epileptogenesis. Kindling model was established in male Wistar rats by intraperitoneal (i.p.) administration of PTZ (30 mg/kg) on every alternate day till the animal became fully kindled or till 6 weeks. Three doses of BBR (50, 100, and 200 mg/kg) and nano-BBR (25, 50, 100 mg/kg) were studied for seizure score, percentage of animal kindled, histopathological score, oxidative stress, inflammation, and apoptosis in PTZ treated rats by conducting cytokines, gene expression and protein expression analysis. BBR nanoparticles showed significant effect on the seizure score and percentage of animal kindled, histopathological score, neurobehavioral parameters (Forced swim test, Rotarod), oxidative (MDA, SOD, GSH, GPx) and inflammatory (IL-1beta, TNF-alpha) parameters, apoptotic parameters (Bax and iNOS), and gene (Nrf2, NQO1, HO1) and protein expression (Nrf2) as compared to both PTZ and BBR. BBR nanoparticles showed neuroprotective effect in PTZ induced kindling model of epileptogenesis and proves to be a promising antiepileptogenic therapy for the patients who are at high risk of developing seizures.


Assuntos
Berberina , Excitação Neurológica , Fármacos Neuroprotetores , Masculino , Ratos , Animais , Pentilenotetrazol/toxicidade , Berberina/farmacologia , Berberina/uso terapêutico , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Fator 2 Relacionado a NF-E2/metabolismo , Ratos Wistar , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Anticonvulsivantes/farmacologia , Anticonvulsivantes/uso terapêutico
5.
Curr Drug Deliv ; 20(8): 1049-1066, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35578879

RESUMO

With the advent of ivermectin, tremendous improvement in public health has been observed, especially in the treatment of onchocerciasis and lymphatic filariasis that created chaos mostly in rural, sub-Saharan Africa and Latin American countries. The discovery of ivermectin became a boon to millions of people that had suffered in the pandemic and still holds its pharmacological potential. Ivermectin continued to surprise scientists because of its notable role in the treatment of various other tropical diseases (Chagas, leishmaniasis, worm infections, etc.) and is viewed as the safest drug with the least toxic effects. The current review highlights its role in unexplored avenues towards forging ahead of the repositioning of this multitargeted drug in cancer, viral (the evaluation of the efficacy of ivermectin against SARS-Cov-2 is under investigation) and bacterial infection and malaria. This article also provides a glimpse of regulatory considerations of drug repurposing and current formulation strategies. Due to its broad-spectrum activity, multitargeted nature and promising efforts are put towards the repurposing of this drug throughout the field of medicine. This single drug originated from a microbe, changed the face of global health by proving its unmatched success and progressive efforts continue in maintaining its bequestnin the management of global health by decreasing the burden of various diseases worldwide.


Assuntos
COVID-19 , Oncocercose , Humanos , Ivermectina/uso terapêutico , Reposicionamento de Medicamentos , SARS-CoV-2 , Oncocercose/tratamento farmacológico
6.
Asian J Neurosurg ; 17(2): 274-279, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36120630

RESUMO

Context The aim of the study was to develop a prognostic model using artificial intelligence for patients undergoing lumbar spine surgery for degenerative spine disease for change in pain, functional status, and patient satisfaction based on preoperative variables included in following categories-sociodemographic, clinical, and radiological. Methods and Materials A prospective cohort of 180 patients with lumbar degenerative spine disease was included and divided into three classes of management-conservative, decompressive surgery, and decompression with fixation. Preoperative variables, change in outcome measures (visual analog scale-VAS, Modified Oswestry Disability Index-MODI, and Neurogenic Claudication Outcome Score-NCOS), and type of management were assessed using Machine Learning models. These were used for creating a predictive tool for deciding the type of management that a patient should undergo to achieve the best results. Multivariate logistic regression was also used to identify prognostic factors of significance. Results The area under the curve (AUC) was calculated from the receiver-operating characteristic (ROC) analysis to evaluate the discrimination capability of various machine learning models. Random Forest Classifier gave the best ROC-AUC score in all three classes (0.863 for VAS, 0.831 for MODI, and 0.869 for NCOS), and the macroaverage AUC score was found to be 0.842 suggesting moderate discriminatory power. A graphical user interface (GUI) tool was built using the machine learning algorithm thus defined to take input details of patients and predict change in outcome measures. Conclusion This study demonstrates that machine learning can be used as a tool to help tailor the decision-making process for a patient to achieve the best outcome. The GUI tool helps to incorporate the study results into active decision-making.

7.
J Control Release ; 349: 1009-1030, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35961470

RESUMO

World Health Organisation (WHO) delineated cancer as one of the foremost reasons for mortality with 10 million deaths in the year 2020. Early diagnosis and effective drug delivery are of utmost importance in cancer management. The entrapment of both bio-imaging dyes and drugs will open novel avenues in the area of tumor theranostics. Elevated levels of reactive oxygen species (ROS) and glutathione (GSH) are the characteristic features of the tumor microenvironment (TME). Researchers have taken advantage of these specific TME features in recent years to develop micelle-based theranostic nanosystems. This review focuses on the advantages of redox-sensitive micelles (RSMs) and supramolecular self-assemblies for tumor theranostics. Key chemical linkers employed for the tumor-specific release of the cargo have been discussed. In vitro characterisation techniques used for the characterization of RSMs have been deliberated. Potential bottlenecks that may present themselves in the bench-to-bedside translation of this technology and the regulatory considerations have been deliberated.


Assuntos
Micelas , Neoplasias , Corantes , Glutationa/metabolismo , Humanos , Neoplasias/tratamento farmacológico , Oxirredução , Espécies Reativas de Oxigênio , Nanomedicina Teranóstica/métodos , Microambiente Tumoral
8.
Geophys Res Lett ; 49(7): e2021GL097472, 2022 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-35601504

RESUMO

This study investigates selected secondary atmospheric responses to the widely reported emission change attributed to COVID-19 lockdowns in the highly polluted Indo-Gangetic Plain (IGP) using ground-based measurements of trace gases and particulate matter. We used a chemical box-model to show that production of nighttime oxidant, NO3, was affected mainly by emission decrease (average nighttime production rates 1.2, 0.8 and 1.5 ppbv hr-1 before, during and relaxation of lockdown restrictions, respectively), while NO3 sinks were sensitive to both emission reduction and seasonal variations. We have also shown that the maximum potential mixing ratio of nitryl chloride, a photolytic chlorine radical source which has not been previously considered in the IGP, is as high as 5.5 ppbv at this inland site, resulting from strong nitrate radical production and a potentially large particulate chloride mass. This analysis suggests that air quality measurement campaigns and modeling explicitly consider heterogeneous nitrogen oxide and halogen chemistry.

9.
Drug Discov Today ; 27(8): 2137-2150, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35489675

RESUMO

Biofilms are sessile communities of microorganisms, mainly bacteria, that grow on biotic and abiotic surfaces. These microorganisms are embedded within an extracellular polymeric substance that provides enhanced protection from antimicrobials. Chronic wounds provide an ideal habitat for biofilm formation. Bacteria can easily attach to wound debris and can infect the wound due to an impaired host immune response. This review highlights the mechanism of biofilm formation and the role of biofilms in the pathophysiology of chronic wounds. Our major focus is on various formulation strategies and delivery systems that are employed to eradicate or disperse biofilms, thereby effectively managing acute and chronic wounds. We also discuss clinical research that has studied or is studying the treatment of biofilm-infected chronic wounds.


Assuntos
Antibacterianos , Matriz Extracelular de Substâncias Poliméricas , Infecção dos Ferimentos , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Bactérias/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Humanos , Infecção dos Ferimentos/tratamento farmacológico , Infecção dos Ferimentos/microbiologia
10.
Faraday Discuss ; 229: 89-107, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33735341

RESUMO

Photoelectrochemical (PEC) splitting of water to make hydrogen is a promising clean-energy technology. The oxygen evolution reaction (OER) largely determines the energy efficiency in PEC water-splitting. Hematite, which is a cheap and sustainable semiconductor material with excellent chemical properties, a favourable band gap (2.1 eV) and composed of earth abundant elements is a suitable model photoanode material for studying OER. To understand the design of energy efficient anodes, it is highly desirable to have mechanistic insight into OER at an atomistic level which can be directly connected to experimentally measured quantities. We present a multiscale computational model of OER which connects the thermodynamics and kinetics of elementary charge transfer reactions in OER to kinetics of OER at laboratory length and time scales. We couple density functional theory (DFT) and DFT based molecular dynamics (DFT-MD) simulations with solvent effects at an atomistic level with kinetic Monte Carlo (kMC) simulations at a coarse-grained level in our multiscale model. The time and applied bias potential dependent surface coverage, which are experimentally not known, and the O2 evolution rate during OER at the hematite-water interface are calculated by the multiscale model. Furthermore, the multiscale model demonstrates the effect of explicitly modelling the interaction of water with the electrode surface via direct adsorption.

11.
Sci Total Environ ; 751: 141728, 2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-32890797

RESUMO

Trees significantly impact land-atmosphere feedbacks through evapotranspiration, photosynthesis and isoprene emissions. These processes influence the local microclimate, air quality and can mitigate temperature extremes and sequester carbon dioxide. Despite such importance, currently only 5 out of 15 atmospheric chemistry climate models even partially account for the presence of cropland trees. We first show that the tree cover over intensely farmed regions in Asia, Australia and South America is significantly underestimated (e.g. only 1-3% tree cover over north-India) in the Model of Emissions of Gases and Aerosol from Nature (MEGAN) and absent in Noah land-surface module of the Weather Research and Forecasting (WRF-Chem) Model. By including the actual tree cover (~10%) over the north-west Indo Gangetic Plain in the Noah land-surface module of the WRF-Chem and the MEGAN module, during the rice growing monsoon season in August, we find that the latent heat flux alone increases by 100%-300% while sensible heat flux reduces by 50%-100%, leading to a reduction in daytime boundary layer height by 200-400 m. This greatly improves agreement between the modelled and measured temperature, boundary layer height and surface ozone, which were earlier overestimated and isoprene and its oxidation products which were earlier underestimated. Mitigating peak daytime temperatures and ozone improves rice production by 10 to 20%. Our findings from north west Indo-Gangetic Plain establish that such plantations mitigate heat stress, and have beneficial effects on crop yields while also sequestering carbon. Expanding agroforestry practices to 50% of the cropland area could result in up to 40% yield gain regionally. Implementing such strategies globally could increase crop production and sequester 0.3-30 GtC per year, and therefore future climate mitigation and food security efforts should consider stakeholder participation for increased cropland agroforestry in view of its beneficial effects.


Assuntos
Poluentes Atmosféricos , Ozônio , Poluentes Atmosféricos/análise , Ásia , Atmosfera , Austrália , Produtos Agrícolas , Monitoramento Ambiental , Índia , Ozônio/análise , América do Sul , Temperatura , Árvores
12.
Int J Pharm ; 594: 120129, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33271310

RESUMO

Aim of the study was to reduce the dose and dosing frequency of duloxetine HCl (DXT) by complexation with sulfobutylether-ß-cyclodextrin (SBEßCD), an anionic cyclodextrin through permeation enhancement for more effective management of depression. Spray dried inclusion complexes of drug with SBEßCD were prepared and incorporated in medicated patches followed by their ex vivo permeation and skin retention studies. Then, in vivo efficacy and absorption of the drug from developed optimised patch was determined in Wistar rats by administering drug through oral route (free drug) and transdermal route (complexed drug). Swimming, immobility and climbing parameters in FST while ambulation and rearings parameters in LAT test were assessed. Addition of permeation enhancer (PE) increased drug permeation and the enhancement ratio (ER) was 3.05 and 1.67 for the patch having complexed DXT and spray dried sample of DXT in comparison to free DXT respectively. The amount of drug retained in skin and in optimized medicated patch after 72 h was relatively lower compared to the formulation having free DXT. Enhanced antidepressive activity was observed for complexed drug compared to free drug. We believe that spray dried complexation based transdermal patch can serve as potential innovative drug delivery system for DXT.


Assuntos
Depressão , Absorção Cutânea , Administração Cutânea , Animais , Cloridrato de Duloxetina , Ratos , Ratos Wistar , Pele/metabolismo , Adesivo Transdérmico , beta-Ciclodextrinas
13.
Acta Neurochir (Wien) ; 163(2): 423-440, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33354733

RESUMO

BACKGROUND: Due to the lack of high-quality evidence which has hindered the development of evidence-based guidelines, there is a need to provide general guidance on cranioplasty (CP) following traumatic brain injury (TBI), as well as identify areas of ongoing uncertainty via a consensus-based approach. METHODS: The international consensus meeting on post-traumatic CP was held during the International Conference on Recent Advances in Neurotraumatology (ICRAN), in Naples, Italy, in June 2018. This meeting was endorsed by the Neurotrauma Committee of the World Federation of Neurosurgical Societies (WFNS), the NIHR Global Health Research Group on Neurotrauma, and several other neurotrauma organizations. Discussions and voting were organized around 5 pre-specified themes: (1) indications and technique, (2) materials, (3) timing, (4) hydrocephalus, and (5) paediatric CP. RESULTS: The participants discussed published evidence on each topic and proposed consensus statements, which were subject to ratification using anonymous real-time voting. Statements required an agreement threshold of more than 70% for inclusion in the final recommendations. CONCLUSIONS: This document is the first set of practical consensus-based clinical recommendations on post-traumatic CP, focusing on timing, materials, complications, and surgical procedures. Future research directions are also presented.


Assuntos
Lesões Encefálicas Traumáticas/cirurgia , Conferências de Consenso como Assunto , Craniotomia/normas , Procedimentos de Cirurgia Plástica/normas , Humanos , Hidrocefalia/cirurgia , Itália
14.
J Pharm Sci ; 110(5): 2185-2195, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33383057

RESUMO

Schizophrenia is a neurodevelopmental disorder which is expressed in the form of disturbed behaviour and abnormal mental functions. Patient's non-adherence to the medicine is the main cause of failure of drug therapy and increases incidence of relapses. Thus, for successful management of disease long acting parenteral formulations were developed. Aripiprazole was encapsulated in biocompatible polycaprolactone microsphere by o/w emulsion solvent-evaporation method in order to achieve sustained release of the drug for several weeks after single subcutaneous administration. They were optimised on the basis of various parameters such as physical appearance, particle size (49.4 µm-387.1 µm), encapsulation efficiency (70%-95%), percentage yield (33%-75%) and drug loading (25.9%-47.5%). The surface topography and sphericity of the microspheres was determined by scanning electron microscopy which revealed that the microspheres formed were spherical and non-porous in nature. The in vitro releases from the selected formulations were found to be 87% and 95% respectively after 45 days of dissolution. In vivo efficacy of optimised formulation showed significantly (p < 0.05) amelioration of various positive, negative and cognitive symptoms associated with schizophrenia and oxidative stress markers in ketamine-induced schizophrenia model in rats for 30 days.


Assuntos
Esquizofrenia , Animais , Aripiprazol , Preparações de Ação Retardada , Ácido Láctico , Microscopia Eletrônica de Varredura , Microesferas , Tamanho da Partícula , Poliésteres , Ratos , Esquizofrenia/tratamento farmacológico
15.
Environ Pollut ; 267: 115538, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33254592

RESUMO

Isoprene, formaldehyde and acetaldehyde are important reactive organic compounds which strongly impact atmospheric oxidation processes and formation of tropospheric ozone. Monsoon meteorology and the topography of Himalayan foothills cause surface emissions to get rapidly transported both horizontally and vertically, thereby influencing atmospheric processes in distant regions. Further in monsoon, Indo-Gangetic Plain is a major rice growing region of the world and daytime hourly ozone can frequently exceed phytotoxic dose of 40 ppb O3. However, the sources and ambient variability of these compounds which are potent ozone precursors are unknown. Here, we investigate the sources and photochemical processes driving their emission/formation during monsoon season from a sub-urban site at the foothills of the Himalayas. The measurements were performed in July, August and September using a high sensitivity mass spectrometer. Average ambient mixing ratios (±1σ variability) of isoprene, formaldehyde, acetaldehyde, and the sum of methyl vinyl ketone and methacrolein (MVK+MACR), were 1.4 ± 0.3 ppb, 5.7 ± 0.9 ppb, 4.5 ± 2.0 ppb, 0.75 ± 0.3 ppb, respectively, and much higher than summertime values in May. For isoprene these values were comparable to mixing ratios observed over tropical forests. Surprisingly, despite occurrence of anthropogenic emissions, biogenic emissions were found to be the major source of isoprene with peak daytime isoprene driven by temperature (r ≥ 0.8) and solar radiation. Photo-oxidation of precursor hydrocarbons were the main sources of acetaldehyde, formaldehyde and MVK+MACR. Ambient mixing ratios of all the compounds correlated poorly with acetonitrile (r ≤ 0.2), a chemical tracer for biomass burning suggesting negligible influence of biomass burning during monsoon season. Our results suggest that during monsoon season when radiation and rain are no longer limiting factors and convective activity causes surface emissions to be transported to upper atmosphere, biogenic emissions can significantly impact the remote upper atmosphere, climate and ozone affecting rice yields.


Assuntos
Poluentes Atmosféricos , Ozônio , Acetaldeído , Butadienos , Monitoramento Ambiental , Formaldeído , Hemiterpenos , Índia , Estações do Ano
16.
Int J Pharm ; 586: 119439, 2020 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-32622808

RESUMO

Mirtazapine, an antidepressant drug has been proved to exert antipruritic effect upon oral administration in numerous clinical trial studies. The objective of the current study was to develop mirtazapine loaded solid lipid nanoparticles (SLNs) and evaluate its potential as a topical drug delivery system for management of pruritus. Mirtazapine loaded SLNs were successfully developed and optimized applying Box-Behnken design. The optimized mirtazapine loaded SLNs were characterized for physicochemical parameters and morphology. The in vitro cytotoxicity and cellular uptake studies of optimized SLNs were performed in human epithelial A-431 cell line. Further, the optimized mirtazapine loaded SLNs dispersion was incorporated into gel and characterized for rheology and texture analysis. The particle size and PDI of optimized mirtazapine loaded was found to be 180.3 nm and 0.209 respectively. The cytotoxicity studies revealed the safety of mirtazapine loaded SLNs on topical administration. The developed gel showed pseudoplastic flow behavior and good textural profile. The in vitro drug release studies showed that the developed mirtazapine loaded SLNs dispersion and its gel followed Korsmeyer-Peppas model (R2 = 0.905) and Higuchi model (R2 = 0.928) respectively. The ex vivo drug permeation studies showed higher values for mean cumulative amount of drug released (548.25 ± 29.29 µg/cm2), permeation flux (45.10 ± 0.78 µg/cm2/h) and skin retention (11.33 ± 0.85%) of SLNs gel in comparison to pure drug gel. The stability studies indicate the stability of SLNs gel for three months at refrigerated and ambient temperatures. Therefore, abovementioned findings suggest that mirtazapine loaded SLNs could be a potential system for topical management of pruritus.


Assuntos
Antidepressivos/administração & dosagem , Sistemas de Liberação de Medicamentos , Mirtazapina/administração & dosagem , Nanopartículas , Administração Cutânea , Animais , Antidepressivos/farmacocinética , Antidepressivos/toxicidade , Linhagem Celular , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Armazenamento de Medicamentos , Humanos , Lipídeos/química , Mirtazapina/farmacocinética , Mirtazapina/toxicidade , Tamanho da Partícula , Prurido/tratamento farmacológico , Ratos , Ratos Wistar , Absorção Cutânea , Temperatura
17.
Drug Dev Ind Pharm ; 46(6): 931-945, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32420753

RESUMO

Aim: The aim of this work was to develop buccoadhesive tablets for the systemic delivery of duloxetine HCl (DXT) using more soluble derivatives of ß-cyclodextrin, i.e. hydroxypropyl-ß-cyclodextrin (HPßCD) and sulfobutylether-ß-cyclodextrin (SBEßCD) and to investigate enhanced cellular uptake of inclusion complexed drug.Materials and methods: Freeze dried and spray dried complexes of both cyclodextrin derivatives with DXT (1:1 molar) were prepared and characterized with DSC, FTIR, and PXRD techniques. C971 and PC, on the basis of swelling behavior, erosion and in vitro residence time, were selected for further study at different levels (-1, 0, +1) to optimize the formulation in terms of enhanced drug release and ex vivo permeation.Results: SBEßCD based complexes show more aqueous solubility of DXT (0.782 and 0.958 mM) and more complexation efficiency compared to HPßCD at 25 °C and 37 °C, respectively. Apparent stability constant was reported to be higher (1109.94 and 1693.25 M-1) for DXT-SBEßCD at 25 °C and 37 °C, respectively, than the corresponding values for DXT-HPßCD systems. Enhanced cellular uptake using fibroblast cells was revealed for complexed drug compared to free drug .Conclusion: Both cyclodextrin derivatives are able to enhance drug release and permeation in vitro and ex vivo.


Assuntos
2-Hidroxipropil-beta-Ciclodextrina/química , Ciclodextrinas , Cloridrato de Duloxetina/química , Administração Bucal , Solubilidade
18.
Environ Sci Technol ; 54(8): 4790-4799, 2020 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-32189491

RESUMO

Elevated PM2.5 concentrations frequently cause severe air pollution events in Delhi. Till recently, the effect of crop residue burning on the air quality in Delhi has not been fully quantified and the approaches to control the impact of fire emissions have not been effective. In this study, for the first time, we quantified the statewise contribution of post-monsoon crop residue burning in the northwestern states of India to surface PM2.5 concentrations in Delhi using several sensitivity experiments with the Weather Research and Forecasting model coupled with Chemistry (WRF-Chem) and FINNv1.5 fire emission inventory. Results were evaluated with ground-based observations in Delhi (21 stations), Punjab, and Haryana (14 stations). On average, ∼20% of PM2.5 concentration in Delhi during the post-monsoon season (October-November) was found to be contributed by nonlocal fire emissions. However, on typical air pollution events, fire emissions contributed as high as 50-75% (80-120 µg/m3) to PM2.5 in Delhi, highlighting the importance of both external transport and local emissions to PM2.5 pollution in Delhi.


Assuntos
Poluentes Atmosféricos/análise , Poluição do Ar/análise , Monitoramento Ambiental , Índia , Material Particulado/análise
19.
AAPS PharmSciTech ; 21(2): 43, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31897806

RESUMO

Methicillin-resistant Staphylococcus aureus (MRSA) is considered a common colonizer of burn wound and accounts for high morbidity and mortality all across the globe. Systemic antibiotic therapy which is generally prescribed for these patients has a number of limitations. These include high drug dose, toxicity, and chances of development of drug resistance. However, local delivery of drug not only addresses these limitations but also provides better efficacy at the site of infection. In the present study, hydrogel preparations were developed for the topical delivery of moxifloxacin for the treatment of S. aureus-infected burn wound. Moxifloxacin was characterized by UV, FTIR, DSC, hot-stage microscopy, NMR, and HPLC and loaded into conventional and Boswellia-containing novel gels. Gels were characterized by visual examination, pH, UV spectroscopy, and release assays. In vivo studies showed that both gels were effective in eradicating the bacteria completely from the wound site when treatment was started during the early stage of infection. On the contrary, delayed treatment of planktonic and biofilm cells with novel gel showed better efficacy as compared with conventional gel in S. aureus-infected burn wound. Histopathological analysis also showed better skin healing efficacy of novel gel than conventional gel. Our results show that moxifloxacin can be efficiently used topically in the management of burn wound infections along with other antibacterial agents. Since biofilm-mediated infections are on the rise especially in chronic bacterial disease, therefore, a preparation containing antibiofilm agent-like Boswellia as one of the excipients would be more meaningful.


Assuntos
Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Anti-Infecciosos Locais/administração & dosagem , Anti-Infecciosos Locais/farmacologia , Biofilmes/efeitos dos fármacos , Queimaduras/complicações , Quitosana/química , Hidrogéis/química , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Infecção dos Ferimentos/tratamento farmacológico , Animais , Antibacterianos/química , Anti-Infecciosos Locais/química , Boswellia/química , Composição de Medicamentos , Géis , Staphylococcus aureus Resistente à Meticilina , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Moxifloxacina/administração & dosagem , Moxifloxacina/química , Moxifloxacina/uso terapêutico , Infecções Estafilocócicas/microbiologia , Infecção dos Ferimentos/microbiologia
20.
Arch Womens Ment Health ; 23(1): 113-122, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-30798377

RESUMO

The relation between schizophrenia and the menstrual cycle has always been found attractive by researchers. It is still a question of debate whether the clinical picture changes during the menstrual cycle. Our study aimed to see whether there is any change of symptoms during different phases of menstrual cycle (premenstrual, menstrual, and postmenstrual) in patients suffering from schizophrenia. Over a period of 15 months, 40 female inpatients of a tertiary care psychiatric hospital with the diagnosis of schizophrenia were assessed by applying PANSS. Rating was done up to two menstrual cycles. Total scores, positive and negative subscale scores, and general psychopathology scores of PANSS in premenstrual, menstrual, and postmenstrual phases of those patients were compared with one another by applying paired t test. Symptoms in women suffering from schizophrenia frequently vary with the different phases of menstrual cycle. The positive symptoms improved significantly only during progesterone phase. Negative symptoms and general psychopathology subscale showed improvement on estrogen phases of menstrual cycle. So optimal treatment needs to be adjusted to the individual women suffering from schizophrenia.


Assuntos
Ciclo Menstrual/psicologia , Esquizofrenia/fisiopatologia , Adulto , Estrogênios/metabolismo , Feminino , Humanos , Índia , Pacientes Internados , Progesterona/metabolismo , Estudos Prospectivos , Escalas de Graduação Psiquiátrica , Psicologia do Esquizofrênico
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