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1.
J Hazard Mater ; 472: 134475, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38733781

ABSTRACT

Narrow spectrum nano-antibiotics are supposedly the future trouble-shooters to improve the efficacy of conventional antimicrobials for treatment of severe bacterial infections, remove contamination from water and diminish the development of antibiotic resistance. In this study, antimicrobial peptide functionalized boron-carbon-nitride nanosheets ((Ant)pep@BCN NSs) are developed that are a promising wastewater disinfector and antibiotic resistant bactericide agent. These nanosheets are developed for selective removal and effective inactivation of antibiotic resistant bacteria (ARB) from water in presence of two virulent bacteria. The (Ant)pep@BCN NSs provide reactive surface receptors specific to the ARB. They mimic muralytic enzymes to damage the cell membrane of ARB. These NSs demonstrate 3-fold higher antimicrobial efficiency against the targeted ARB compared to pristine BCN even at lower concentrations. To the best of our knowledge, this is the first time that functionalized BCN has been developed to remove ARB selectively from wastewater. Furthermore, the (Ant)pep@BCN selectively reduced the microbiological load and led to morphological changes in Gram negative ARB in a mixed bacterial inoculum. These ARBs excreted outer-inner membrane vesicles (OIMVs) of triangular shape as a stimuli response to (Ant)pep@BCN NSs. These novel antimicrobial peptide-NSs have potential to improve treatment efficacy against ARB infections and water contamination.


Subject(s)
Anti-Bacterial Agents , Water Purification , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Water Purification/methods , Wastewater/chemistry , Nanostructures/chemistry , Antimicrobial Peptides/pharmacology , Antimicrobial Peptides/chemistry , Water Pollutants, Chemical/chemistry , Drug Resistance, Bacterial/drug effects , Boron Compounds/chemistry , Boron Compounds/pharmacology
2.
ACS Appl Bio Mater ; 7(2): 892-908, 2024 02 19.
Article in English | MEDLINE | ID: mdl-38253516

ABSTRACT

In this study, we have synthesized a bioactive glass with composition 45SiO2-20Na2O-23CaO-6P2O5-2.5B2O3-1ZnO-2MgO-0.5CaF2 (wt %). Further, it has been incorporated with 0.4 wt % iron carbide nanoparticles to prepare magnetic bioactive glass (MBG) with good heat generation capability for potential applications in magnetic field-assisted hyperthermia. The MBG scaffolds have been fabricated using extrusion-based additive manufacturing by mixing MBG powder with 25% Pluronic F-127 solution as the binder. The saturation magnetization of iron carbide nanoparticles in the bioactive glass matrix has been found to be 80 emu/g. The morphological analysis (pore size distribution, porosity, open pore network modeling, tortuosity, and pore interconnectivity) was done using an in-house developed methodology that revealed the suitability of the scaffolds for bone tissue engineering. The compressive strength (14.3 ± 1.6 MPa) of the MBG scaffold was within the range of trabecular bone. The in vitro test using simulated body fluid (SBF) showed the formation of apatite indicating the bioactive nature of scaffolds. Further, the drug delivery behaviors of uncoated and polycaprolactone (PCL) coated MBG scaffolds have been evaluated by loading an anticancer drug (Mitomycin C) onto the scaffolds. While the uncoated scaffold demonstrated the drug's burst release for the initial 80 h, the PCL-coated scaffold showed the gradual release of the drug. These results demonstrate the potential of the proposed MBG for bone tissue engineering and drug delivery applications.


Subject(s)
Carbon Compounds, Inorganic , Iron Compounds , Tissue Engineering , Tissue Scaffolds , Tissue Engineering/methods , Glass , Bone and Bones
3.
ACS Appl Bio Mater ; 6(12): 5210-5223, 2023 Dec 18.
Article in English | MEDLINE | ID: mdl-37955988

ABSTRACT

Conventional three-dimensional (3D)-printed hydroxyapatite (HA)-based constructs have limited utility in bone tissue engineering due to their poor mechanical properties, elevated risk of microbial infection, and limited pore interconnectivity. 3D printing of complex multiple components to fabricate fully interconnected scaffolds is a challenging task; here, in this work, we have developed a procedure for fabrication of printable ink for complex systems containing multinanomaterials, i.e., HAACZ (containing 1 wt % Ag, 4 wt % CeO2, and 6 wt % ZnO) with better shear thinning and shape retention properties. Moreover, 3D-printed HAACZ scaffolds showed a modulus of 143.8 GPa, a hardness of 10.8 GPa, a porosity of 59.6%, effective antibacterial properties, and a fully interconnected pore network to be an ideal construct for bone healing. Macropores with an average size of ∼469 and ∼433 µm within the scaffolds of HA and HAACZ and micropores with an average size of ∼0.6 and ∼0.5 µm within the strut of HA and HAACZ were developed. The distribution of fully interconnected micropores was confirmed using computerized tomography, whereas the distribution of micropores within the strut was visualized using Voronoi tessellation. The water contact angle studies revealed the most suitable hydrophilic range of water contact angles of ∼71.7 and ∼76.6° for HA and HAACZ, respectively. HAACZ scaffolds showed comparable apatite formation and cytocompatibility as that of HA. Antibacterial studies revealed effective antibacterial properties for the HAACZ scaffold as compared to HA. There was a decrease in bacterial cell density for HAACZ from 1 × 105 to 1.2 × 103 cells/mm2 against Gram-negative (Escherichia coli) and from 1.9 × 105 to 5.6 × 103 bacterial cells/mm2 against Gram-positive (Staphylococcus aureus). Overall, the 3D-printed HAACZ scaffold resulted in mechanical properties, comparable to those of the cancellous bone, interconnected macro- and microporosities, and excellent antibacterial properties, which could be utilized for bone healing.


Subject(s)
Durapatite , Zinc Oxide , Durapatite/pharmacology , Biocompatible Materials , Tissue Scaffolds , Zinc Oxide/pharmacology , Anti-Bacterial Agents/pharmacology , Printing, Three-Dimensional , Water
4.
Resuscitation ; 191: 109903, 2023 10.
Article in English | MEDLINE | ID: mdl-37423492

ABSTRACT

INTRODUCTION: Cognitive activity and awareness during cardiac arrest (CA) are reported but ill understood. This first of a kind study examined consciousness and its underlying electrocortical biomarkers during cardiopulmonary resuscitation (CPR). METHODS: In a prospective 25-site in-hospital study, we incorporated a) independent audiovisual testing of awareness, including explicit and implicit learning using a computer and headphones, with b) continuous real-time electroencephalography(EEG) and cerebral oxygenation(rSO2) monitoring into CPR during in-hospital CA (IHCA). Survivors underwent interviews to examine for recall of awareness and cognitive experiences. A complementary cross-sectional community CA study provided added insights regarding survivors' experiences. RESULTS: Of 567 IHCA, 53(9.3%) survived, 28 of these (52.8%) completed interviews, and 11(39.3%) reported CA memories/perceptions suggestive of consciousness. Four categories of experiences emerged: 1) emergence from coma during CPR (CPR-induced consciousness [CPRIC]) 2/28(7.1%), or 2) in the post-resuscitation period 2/28(7.1%), 3) dream-like experiences 3/28(10.7%), 4) transcendent recalled experience of death (RED) 6/28(21.4%). In the cross-sectional arm, 126 community CA survivors' experiences reinforced these categories and identified another: delusions (misattribution of medical events). Low survival limited the ability to examine for implicit learning. Nobody identified the visual image, 1/28(3.5%) identified the auditory stimulus. Despite marked cerebral ischemia (Mean rSO2 = 43%) normal EEG activity (delta, theta and alpha) consistent with consciousness emerged as long as 35-60 minutes into CPR. CONCLUSIONS: Consciousness. awareness and cognitive processes may occur during CA. The emergence of normal EEG may reflect a resumption of a network-level of cognitive activity, and a biomarker of consciousness, lucidity and RED (authentic "near-death" experiences).


Subject(s)
Cardiopulmonary Resuscitation , Heart Arrest , Out-of-Hospital Cardiac Arrest , Humans , Consciousness , Cardiopulmonary Resuscitation/methods , Prospective Studies , Cross-Sectional Studies , Death , Biomarkers
5.
Biofabrication ; 15(2)2023 02 14.
Article in English | MEDLINE | ID: mdl-36716495

ABSTRACT

Vascularization is an indispensable requirement for fabricating large solid tissues and organs. The natural vasculature derived from medical imaging modalities for large tissues and organs are highly complex and convoluted. However, the present bioprinting capabilities limit the fabrication of such complex natural vascular networks. Simplified bioprinted vascular networks, on the other hand, lack the capability to sustain large solid tissues. This work proposes a generalized and adaptable numerical model to design the vasculature by utilizing the tissue/organ anatomy. Starting with processing the patient's medical images, organ structure, tissue-specific cues, and key vasculature tethers are determined. An open-source abdomen magnetic resonance image dataset was used in this work. The extracted properties and cues are then used in a mathematical model for guiding the vascular network formation comprising arterial and venous networks. Next, the generated three-dimensional networks are used to simulate the nutrient transport and consumption within the organ over time and the regions deprived of the nutrients are identified. These regions provide cues to evolve and optimize the vasculature in an iterative manner to ensure the availability of the nutrient transport throughout the bioprinted scaffolds. The mass transport of six components of cell culture media-glucose, glycine, glutamine, riboflavin, human serum albumin, and oxygen was studied within the organ with designed vasculature. As the vascular structure underwent iterations, the organ regions deprived of these key components decreased significantly highlighting the increase in structural complexity and efficacy of the designed vasculature. The numerical method presented in this work offers a valuable tool for designing vascular scaffolds to guide the cell growth and maturation of the bioprinted tissues for faster regeneration post bioprinting.


Subject(s)
Bioprinting , Tissue Scaffolds , Humans , Tissue Scaffolds/chemistry , Tissue Engineering/methods , Bioprinting/methods , Printing, Three-Dimensional
6.
IEEE Trans Nanobioscience ; 21(3): 380-386, 2022 07.
Article in English | MEDLINE | ID: mdl-34029191

ABSTRACT

In this study, carbon nanotube (CNT) reinforced functionally graded bioactive glass scaffolds have been fabricated using additive manufacturing technique. Sol-gel method was used for the synthesis of the bioactive glass. For ink preparation, Pluronic F-127 was used as an ink carrier. The CNT-reinforced scaffolds were coated with the polymer polycaprolactone (PCL) using dip-coating method to improve their properties further by sealing the micro-cracks. The CNT- reinforcement and polymer coating resulted in an improvement in the compressive strength of the additively manufactured scaffolds by 98% in comparison to pure bioactive glass scaffolds. Further, the morphological analysis revealed interconnected pores and their size appropriate for osteogenesis and angiogenesis. Evaluation of the in vitro bioactivity of the scaffolds after immersion in simulated body fluid (SBF) confirmed the formation of hydroxyapatite (HA). Further, the cellular studies showed good cell viability and initiation of osteogensis. These results demonstrate the potential of these scaffolds for bone tissue engineering applications.


Subject(s)
Nanofibers , Polymers , Glass , Tissue Engineering/methods , Tissue Scaffolds
7.
J Nanosci Nanotechnol ; 21(10): 5026-5035, 2021 10 01.
Article in English | MEDLINE | ID: mdl-33875087

ABSTRACT

In this work, the effect of varying content of B2O3 with respect to SiO2 on mechanical and bioactivity properties have been evaluated for borosilicate bioactive glasses containing SiO2, B2O3, CaO and P2O5. The bioactive glasses have been synthesized using the sol-gel technique. The synthesized glasses were characterized by X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy and Field Emission Scanning electron microscopy (FESEM). These bioactive glasses were fabricated as scaffolds by using polymer foam replication method. Subsequently, in vitro bioactivity evaluation of borosilicate bioactive glass was done. Based on the XRD and energy-dispersive X-ray spectroscopy (EDS) results showing good apatite-formation ability when soaked in simulated body fluid (SBF), one of the bioactive glass (BG-B30 containing 30 mol% B2O3) was selected for further study. The compressive strength of the bioactive glass scaffolds was within the range of trabecular bone. However, it was found near the lower limit of the trabecular bone (0.2-12 MPa). Therefore, BG-B30 scaffold was reinforced with carbon nanotubes (CNTs) to allow for mechanical manipulation during tissue engineering applications. The compressive strength increased from 1.05 MPa to 7.42 MPa (a 606% increase) after reinforcement, while the fracture toughness rose from 0.12 MPa √ m to 0.45 MPa √ m (a 275% increase). Additionally, connectivity of the pores in the CNT reinforced BG-B30 scaffolds were evaluated and the pores were found to be well connected. The evaluated properties of the fabricated scaffolds demonstrate their potential as a synthetic graft for possible application in bone tissue engineering.


Subject(s)
Nanotubes, Carbon , Tissue Engineering , Biocompatible Materials , Boron Compounds , Glass , Microscopy, Electron, Scanning , Silicon Dioxide , Spectroscopy, Fourier Transform Infrared , Tissue Scaffolds , X-Ray Diffraction
8.
Soft Matter ; 17(9): 2640-2651, 2021 Mar 11.
Article in English | MEDLINE | ID: mdl-33533365

ABSTRACT

Fractions of dyes, that are used in large quantities for various applications, are lost during the dying process and contaminate water. In order to avoid their harmful effect on human health, boron nitride nanosheets (BNNSs) have been synthesized in this work and their adsorption behavior for the removal of anionic methyl orange (MO) dye from aqueous solution has been reported. The effect of pH, contact time, and initial dye concentration has been investigated on MO to find the optimum pH, equilibrium and adsorption capacity of the synthesized BNNSs. The adsorption kinetics and isotherm models showed that pseudo-second-order (PSO) kinetic and Freundlich isotherm models were being followed during the adsorption, respectively. The experimental maximum adsorption capacity of the synthesized adsorbent was found to be 575.0 mg g-1, which is due to the strong electrostatic attraction between the negatively charged MO and positively charged BNNSs. Furthermore, density functional theory (DFT) calculations have also been performed to investigate the nature and feasibility of the adsorption process, the interactions of MO dye molecules with the adsorbent, and the adsorption capacity of BNNSs. The theoretical and experimental studies suggest that the adsorption process is physical in nature. It was found that negative charge transfer occurred from MO to BNNSs with high chemical potential suggesting high chemical activity and a decrease in band gap after the adsorption process. These theoretical and experimental findings demonstrate the potential of BNNSs as adsorbents for commercial applications.

9.
Resuscitation ; 159: 54-59, 2021 02.
Article in English | MEDLINE | ID: mdl-33385467

ABSTRACT

BACKGROUND: Early prediction of mortality in adults after in-hospital cardiac arrest (IHCA) remains vital to optimizing treatment strategies. Inflammatory cytokines specific to early prognostication in this population have not been well studied. We evaluated whether novel inflammatory cytokines obtained from adults with IHCA helped predict favorable neurologic outcome. METHODS: The study population included adults with IHCA who underwent ACLS-guided resuscitation between March 2014 and May 2019 at an academic tertiary medical center. Peripheral blood samples were obtained within 6, 24, 48, 72, and 96 h of IHCA and analysis of 15 cytokines were performed. The primary outcome of interest was presence of favorable neurologic outcome at hospital discharge, defined as a Glasgow Outcome Score of 4 or 5. RESULTS: Of the 105 adults with IHCA studied, 27 (25.7%) were noted to have survival with a favorable neurologic outcome while 78 (74.3%) did not. Patients who survived with favorable neurologic outcome were more often men (88.9% vs 61.5%, p = 0.008) and had higher rates of ventricular tachyarrhythmias as their initial rhythm (34.6% vs 11.7%, p = 0.018). Levels of interleukin (IL)-6, IL-8, IL-10, and Tumor Necrosis Factor (TNF)-R1 within 6 or 24 h were significantly lower in patients with favorable neurologic outcome compared with those who had unfavorable neurologic outcome. In multivariable analysis, IL-10 levels within 6 h was the only independent predictor of favorable neurologic outcomes [odds ratio (OR) 0.895, 95% confidence interval 0.805-0.996, p = 0.041]. CONCLUSION: In this contemporary observational study of adults with IHCA receiving ACLS-guided resuscitative and post-resuscitative care, inflammatory cytokines specific to early prognostication in adults with IHCA exist. Further larger scale studies examining the association of these inflammatory cytokines with prognosis are warranted.


Subject(s)
Cardiopulmonary Resuscitation , Heart Arrest , Adult , Heart Arrest/therapy , Hospitals , Humans , Male , Patient Discharge , Prognosis
10.
J Control Release ; 328: 286-303, 2020 12 10.
Article in English | MEDLINE | ID: mdl-32861760

ABSTRACT

There are a lot of geometrical and morphological changes that happen in the human eye with age. Primary open-angle glaucoma, which is caused by the increase in intraocular pressure inside the anterior chamber of the eye is also associated with the physiological aging of the eye. Therefore, it is crucial to understand the effects of aging on drug delivery in the human eye when applied topically. Consequently, a numerical model of topical drug delivery for an aging human eye has been developed using commercial software COMSOL Multiphysics in the current study. Three different age groups (young, middle and old) have been considered and the changes in geometrical and tissue properties of different domains of the eye with age have been included in the numerical model. The effect of aging on heat transfer, aqueous humor flow, intraocular pressure and drug concentration in different domains and orientations of the eye have been investigated. Additionally, an attempt has been made to predict the best class of anti-glaucomatic treatment in silico that should be preferred to treat primary open-angle glaucoma effectively. Results illustrate that there is a decrease in the average corneal temperature and an increase in the temperature deviation across the cornea with age. Further, there is a decrease in the aqueous humor flow magnitude in the anterior chamber of the eye and an increase in intraocular pressure in the anterior chamber of older age groups, which leads to primary open-angle glaucoma. The reduced aqueous humor flow leads to increased drug concentration in the anterior chamber as well as iris and reduced drug concentration in the trabecular mesh of the older age groups, thereby affecting the treatment efficacy. Additionally, our simulated results demonstrate that anti-glaucomatic treatments should be more focused on treating the trabecular mesh rather than the ciliary body of the eye.


Subject(s)
Glaucoma, Open-Angle , Pharmaceutical Preparations , Aged , Aging , Aqueous Humor , Glaucoma, Open-Angle/drug therapy , Hot Temperature , Humans , Intraocular Pressure
11.
Proc Inst Mech Eng H ; 234(9): 942-954, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32633667

ABSTRACT

A numerical model of drug delivery from a therapeutic lens in the anterior portion of the human eye has been developed for a more effective treatment plan of primary open-angle glaucoma. The numerical model takes into account the drug diffusion through the therapeutic lens along with heat transfer and aqueous humor flow in different orientations of the human eye (supine (two-dimensional) as well as standing (three-dimensional)). Results illustrate that the drug diffuses through the therapeutic lens to the cornea and is convected into the anterior chamber of the eye due to the temperature gradient across the eye. In addition, eye orientation significantly affects drug delivery with supine orientation providing better and uniform drug exposure in different target regions of the eye as compared to standing in the case of the therapeutic lens. Furthermore, a comparison of the therapeutic efficacy of the therapeutic lens has been done with topical administration and the drug uptake results from both the drug delivery modes have been validated with the experimental data reported in the literature. The developed model may help ophthalmologists to comprehend the transport and retention of different drugs in different domains and orientations of the human eye when administered through a therapeutic lens.


Subject(s)
Glaucoma, Open-Angle , Pharmaceutical Preparations , Cornea , Drug Delivery Systems , Glaucoma, Open-Angle/drug therapy , Humans
12.
J Nanosci Nanotechnol ; 20(10): 6222-6234, 2020 10 01.
Article in English | MEDLINE | ID: mdl-32384972

ABSTRACT

In this study, we report the synthesis and characterization of boron nitride nanosheets (BNNSs), and their application as an adsorbent to remove the cationic dyes methylene blue (MB) and rhodamine B (RhB) from contaminated water. The synthesized adsorbent was characterized by high-resolution transmission electron microscopy (HR-TEM), field emission electron microscopy (FE-SEM), X-ray diffraction (XRD), Fourier transformed infrared spectroscopy (FTIR) and nitrogen adsorption-desorption isotherm. Detailed experiments and analysis were performed on various molar ratios of boron and nitrogen precursors (1:5 to 1:48) to achieve maximize specific surface area of BNNSs. Among all, the samples synthesized with boric acid and urea (1:30) dissolved in water and methanol produced maximum specific surface area (1801.9 m² g-1). Further, the adsorption study was performed in batches by investigating various adsorption parameters such as effect of pH, contact time, adsorbent dose and adsorption isotherm. The pH study revealed that optimum value was found to be at pH 8. It was found through the kinetic study that pseudo-second-order (PSO) kinetic model was followed by the adsorbent during the adsorption of both the dyes. Further, the adsorption isotherm data well fitted with Langmuir isotherm model. The maximum adsorption capacities of MB and RhB were found to be 333.33 and 312.5 mg g-1, respectively. This demonstrates the potential of BNNSs as novel adsorbent for treatment of dye-contaminated water.

13.
ACS Omega ; 5(18): 10301-10314, 2020 May 12.
Article in English | MEDLINE | ID: mdl-32426587

ABSTRACT

We report the application of Fe3O4-functionalized boron nitride nanosheets (BNNS-Fe3O4 nanocomposite) for the remediation of As(III) ions from contaminated water. The specific surface area of the nanocomposite has been found as 179.5 m2 g-1. Due to its superparamagnetic nature at room temperature, the nanocomposite can be easily isolated from the solution under an external magnetic field. For As(III) ions, the maximum adsorption capacity of the nanocomposite is obtained as 30.3 mg g-1, which is approximately 4 times more than that of the bare BNNSs (8.5 mg g-1). The results from density functional theory calculations are also in close agreement with experimental findings and show that As(OH)3 binds more (∼4 times) efficiently to the BNNS-Fe3O4 nanocomposite than the bare BNNSs, implying a 4 times higher adsorption capacity of the nanocomposite. Especially, it is found that the synthesized nanocomposite could lessen the concentration of As(III) ions from 134 to 2.67 ppb in a solution at 25 °C. On increasing the temperature to 35 °C, the level of As(III) ions could be reduced from 556 to 10.29 ppb, which is close to the limit prescribed by the World Health Organization. The adsorbent was easily separable and showed regeneration properties. These outcomes depict the prospect of using BNNS-Fe3O4 nanocomposites as commercial adsorbents for the removal of As(III) ions from contaminated water.

14.
ACS Appl Mater Interfaces ; 11(21): 19017-19028, 2019 May 29.
Article in English | MEDLINE | ID: mdl-31017758

ABSTRACT

It is widely known that the existence of arsenic (As) in water negatively affects humans and the environment. We report the synthesis, characterization, and application of boron nitride nanosheets (BNNSs) and Fe3O4-functionalized BNNS (BNNS-Fe3O4) nanocomposite for removal of As(V) ions from aqueous systems. The morphology, surface properties, and compositions of synthesized nanomaterials were examined using scanning electron microscopy, transmission electron microscopy, X-ray powder diffraction, surface area analysis, zero-point charge, and magnetic moment determination. The BNNS-Fe3O4 nanocomposites have a specific surface area of 119 m2 g-1 and a high saturation magnetization of 49.19 emu g-1. Due to this strong magnetic property at room temperature, BNNS-Fe3O4 can be easily separated in solution by applying an external magnetic field. From the activation energies, it was found that the adsorption of As(V) ions on BNNSs and BNNS-Fe3O4 was due to physical and chemical adsorption, respectively. The maximum adsorption capacity of BNNS-Fe3O4 nanocomposite for As(V) ions has been found to be 26.3 mg g-1, which is 5 times higher than that of unmodified BNNSs (5.3 mg g-1). This closely matches density functional theory simulations, where it is found that binding energies between BNNS-Fe3O4 nanocomposite and As(OH)5 are 5 times higher than those between BNNSs and As(OH)5, implying 5 times higher adsorption capacity of BNNS-Fe3O4 nanocomposite than unmodified BNNSs. More importantly, it was observed that the synthesized BNNS-Fe3O4 nanocomposite could reduce As(V) ion concentration from 856 ppb in a solution to below 10 ppb (>98.83% removal), which is the permissible limit according to World Health Organization recommendations. Finally, the synthesized adsorbent showed both separation and regeneration properties. These findings demonstrate the potential of BNNS-Fe3O4 nanocomposite for commercial application in separation of As(V) ions from potable and waste water streams.

15.
Microvasc Res ; 124: 76-90, 2019 07.
Article in English | MEDLINE | ID: mdl-30923021

ABSTRACT

Systemic administration of chemotherapeutic drugs is widely used in the treatment of cancer. However, a good understanding of drug transport barriers that influence the treatment efficacy is still lacking. In this study, a voxelized numerical model based on dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI) and computational fluid dynamics (CFD) is employed to study the transport and efficacy of three different chemotherapeutic drugs, namely methotrexate, doxorubicin and cisplatin in human brain tumors. DCE-MRI data provides realistic heterogeneous vasculature of the tumor, the permeability of tissue to contrast agent, interstitial volume fraction (porosity) of the tissue and patient-specific arterial input function (AIF). The permeability of tissue to aforementioned drugs is determined by correlating it with the permeability of tissue to the contrast agent. The model is employed to simulate drug concentration in the tissue and compare the effect of heterogeneous vasculature on the distribution of the drugs in the tumor. The drug accumulation is observed to be higher in high permeability areas initially, and in higher porosity areas at later times. Furthermore, it is observed that methotrexate remains in the interstitial space of the tumor in higher concentration for a longer duration as compared to other two drugs, facilitating more tumor cell killing.


Subject(s)
Antineoplastic Agents/metabolism , Brain Neoplasms/metabolism , Cisplatin/metabolism , Doxorubicin/metabolism , Methotrexate/metabolism , Antineoplastic Agents/pharmacokinetics , Biological Transport , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/drug therapy , Brain Neoplasms/pathology , Cisplatin/pharmacokinetics , Computer Simulation , Doxorubicin/pharmacokinetics , Humans , Magnetic Resonance Imaging , Methotrexate/pharmacokinetics , Models, Biological , Permeability
16.
J Nanosci Nanotechnol ; 19(5): 2738-2746, 2019 05 01.
Article in English | MEDLINE | ID: mdl-30501774

ABSTRACT

45S5 Bioglass® has been used quite extensively in the form of particulate as synthetic bone graft. However, 45S5 glass has certain limitations such as difficulty in sintering and slow and partial conversion to hydroxy carbonated apatite. In pursuit of overcoming these limitations, bioactive glasses (13-93B1) containing increased amount of B2O3 by partial replacement of SiO2 have been prepared using sol-gel technique in this study. Since bioactive glasses are brittle in nature, therefore, they are unsuitable for load bearing sites. Consequently, 3D porous scaffolds by reinforcement with varying weight percent of carbon nanotubes (CNTs) have been fabricated in this work by physical mixing and polymer foam replication technique. Compared with pure 13-93B1 bioactive glasses, addition of 0.2 weight percent of CNT resulted in maximum increase in compressive strength from 1.80 MPa to 5.84 MPa (a 224% increase) and elastic modulus from 102 MPa to 269.4 MPa (a 164% increase), respectively. Bioactivity of these scaffolds was confirmed in vitro using simulated body fluid test for 28 days. The compressive strength post-SBF studies were within the range of compressive strength of trabecular bone. These results show potential of fabricating a 3D porous scaffold with sufficient strength and biocompatibility using CNT-1393B1 bioactive glasses.


Subject(s)
Nanotubes, Carbon , Ceramics , Compressive Strength , Glass , Porosity , Silicon Dioxide , Tissue Engineering , Tissue Scaffolds
17.
Curr Neurol Neurosci Rep ; 17(8): 62, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28669033

ABSTRACT

PURPOSE OF REVIEW: Of the approximately 350,000 out-of-hospital, and 750,000 after in-hospital cardiac arrest (CA) events in the US annually approximately 5-9% and 20% respectively may achieve return of spontaneous circulation (ROSC) after attempted cardiopulmonary resuscitation (CPR). Up to 2/3 of these initial survivors may go on die in the subsequent 24-72 hours after ROSC due to a combination of (1) on-going cerebral injury, (2) myocardial dysfunction and (3) massive systemic inflammatory response. In order to successfully manage patients more effectively, monitoring methods are needed to aid clinicians in the detection and quantification of intra-cardiac arrest and post-resuscitation pathophysiological cerebral injury processes in the intensive care unit. RECENT FINDINGS: Over the last few years many modalities have been used for cerebral monitoring during and after CA, these include quantitative pupillometry, transcranial doppler sonography, optic nerve sheath diameter measurements, microdialysis, tissue oxygenation monitoring, intra-cranial pressure monitoring, and electroencephalography. Current studies indicate that these modalities may be used for the purpose of neurological monitoring during cardiac arrest resuscitation as well as in the post-resuscitation period. Multiple overlapping processes, including alterations in cerebral blood flow (CBF), raised intracerebralpressure, disorders of metabolism, imbalanced oxygen delivery and reperfusion injury contribute to cell death during the post-resuscitation period has led to the birth of post-resuscitation management strategies in the 21st century. This review provides a succinct overview of currently available bedside invasive and non-invasive neuro-monitoring methods after CA.


Subject(s)
Brain Diseases/diagnosis , Heart Arrest/complications , Brain Diseases/etiology , Humans
18.
J Colloid Interface Sci ; 463: 180-7, 2016 Feb 01.
Article in English | MEDLINE | ID: mdl-26520825

ABSTRACT

Galvanic replacement of silver (Ag) by platinum (Pt) on bi-metallic nanorods (NRs) having gold (Au) core and silver shell (Au@Ag) resulted in discontinuous coating of Pt over Au (Au@Pt-DC) NRs. However, a novel method has been developed in this work for the preparation of Au NRs having smooth and continuous coating of Pt (Au@Pt-C NRs) using galvanic replacement reaction of Au@Ag NRs in presence of sulphuric acid. Selective blocking by the bisulfate ions that are adsorbed on Pt surface, preventing Pt on Pt deposition seems to be the mechanism of formation of Au@Pt-C NRs. Effect of the nature of Pt shell (i.e. whether continuous or discontinuous) on SERS activity of the NRs was investigated with methylene blue (MB) as a reporter molecule. The specific enhancement of the Raman signals were in the order Au@ Pt-C NRs

19.
J Nanosci Nanotechnol ; 15(3): 1960-72, 2015 Mar.
Article in English | MEDLINE | ID: mdl-26413609

ABSTRACT

Targeted drug delivery with controlled rate is vital for therapeutic purpose especially for cancer therapy. Advanced biomaterials with the aid of nanotechnology have evolved as efficient drug delivery systems (DDS), providing a multi-functional platform for simultaneous therapeutic and diagnostic (theranostic) functions. This review discusses current advances in synthesis and applications of inorganic materials such as quantum dots, carbon nanotubes and graphene oxides for drug delivery. The strategies of surface-functionalization of these inorganic materials to render them biocompatible are also reviewed. The advantages and applications of these biomaterials as multi-functional moiety for bio-imaging, drug targeting and delivery have been discussed. The review concludes with discussion on challenges that limits the practical applications of some materials as a drug carrier for therapeutic use. These issues remain to be fully addressed for their maximum utilization for biomedical applications.


Subject(s)
Drug Carriers , Nanostructures , Animals , Drug Carriers/chemical synthesis , Drug Carriers/chemistry , Humans , Molecular Imaging , Nanostructures/chemistry
20.
Ann Am Thorac Soc ; 11(6): 882-9, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24964265

ABSTRACT

RATIONALE: HIV seropositivity has long been considered a contraindication to lung transplantation, primarily because of the potential risks of added immunosuppression. In the past decade, however, experience with kidney and liver transplantation in the setting of HIV infection, with achievement of satisfactory outcomes, has grown considerably. This promising development has created a need to reconsider this contraindication to lung transplantation. OBJECTIVES: There is presently limited evidence upon which to base medical decision-making regarding lung transplantation in individuals with HIV infection. In our present study, we wished to extend the existing literature by reporting the outcomes of three individuals with HIV infection who underwent lung transplantation at two centers. METHODS: We compiled data for a case series of three HIV-infected subjects undergoing lung transplantation at two centers. MEASUREMENTS AND MAIN RESULTS: We reviewed medical records to investigate the effects of lung transplantation on the course of HIV infection, the development of HIV-related opportunistic infections or malignancies, the occurrence of lung transplant and HIV drug interactions, and the extent of acute rejection. Subject 1, who underwent transplantation for HIV-associated pulmonary arterial hypertension, experienced recalcitrant acute rejection requiring a lymphocyte-depleting agent with subsequent rapid development of bronchiolitis obliterans syndrome. Subjects 2 and 3, who underwent transplantation for idiopathic pulmonary fibrosis, experienced mild acute rejection but remain free from chronic rejection at 4 and 2 years after transplant, respectively. CONCLUSIONS: Lung transplantation may be feasible for carefully selected patients in the setting of controlled HIV infection. On the basis of our experience with three patients, we caution that acute graft rejection may be more common in such patients.


Subject(s)
Bronchiolitis Obliterans/surgery , HIV Seropositivity/complications , Idiopathic Pulmonary Fibrosis/surgery , Lung Transplantation , Adult , Aged , Bronchiolitis Obliterans/complications , Feasibility Studies , Female , Follow-Up Studies , Humans , Idiopathic Pulmonary Fibrosis/complications , Male , Middle Aged
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