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2.
Int J Nanomedicine ; 14: 6073-6101, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31686803

RESUMO

Background: Amphotericin B (AmB) as a liposomal formulation of AmBisome is the first line of treatment for the disease, visceral leishmaniasis, caused by the parasite Leishmania donovani. However, nephrotoxicity is very common due to poor water solubility and aggregation of AmB. This study aimed to develop a water-soluble covalent conjugate of gold nanoparticle (GNP) with AmB for improved antileishmanial efficacy and reduced cytotoxicity. Methods: Citrate-reduced GNPs (~39 nm) were functionalized with lipoic acid (LA), and the product GNP-LA (GL ~46 nm) was covalently conjugated with AmB using carboxyl-to-amine coupling chemistry to produce GNP-LA-AmB (GL-AmB ~48 nm). The nanoparticles were characterized by dynamic light scattering, transmission electron microscopy (TEM), and spectroscopic (ultraviolet-visible and infrared) methods. Experiments on AmB uptake of macrophages, ergosterol depletion of drug-treated parasites, cytokine ELISA, fluorescence anisotropy, flow cytometry, and gene expression studies established efficacy of GL-AmB over standard AmB. Results: Infrared spectroscopy confirmed the presence of a covalent amide bond in the conjugate. TEM images showed uniform size with smooth surfaces of GL-AmB nanoparticles. Efficiency of AmB conjugation was ~78%. Incubation in serum for 72 h showed <7% AmB release, indicating high stability of conjugate GL-AmB. GL-AmB with AmB equivalents showed ~5-fold enhanced antileishmanial activity compared with AmB against parasite-infected macrophages ex vivo. Macrophages treated with GL-AmB showed increased immunostimulatory Th1 (IL-12 and interferon-γ) response compared with standard AmB. In parallel, AmB uptake was ~5.5 and ~3.7-fold higher for GL-AmB-treated (P<0.001) macrophages within 1 and 2 h of treatment, respectively. The ergosterol content in GL-AmB-treated parasites was ~2-fold reduced compared with AmB-treated parasites. Moreover, GL-AmB was significantly less cytotoxic and hemolytic than AmB (P<0.01). Conclusion: GNP-based delivery of AmB can be a better, cheaper, and safer alternative than available AmB formulations.

3.
Molecules ; 24(21)2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31694279

RESUMO

GVL is a green solvent used in Fmoc-based solid-phase peptide synthesis. It is susceptible to ring opening in the presence of bases such as piperidines, which are used to remove the Fmoc protecting group. Here we studied the formation of the corresponding acyl piperidides by time-dependent monitoring using NMR. The results, corroborated by theoretical calculations, indicate that a solution of piperidines in GVL should be prepared daily for a better Fmoc removal.

4.
Protein Pept Lett ; 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31654508

RESUMO

BACKGROUND: Urine is considered one of the biological fluids in which antimicrobial peptides are secreted or expressed. Cow urine has not been investigated for the presence of these peptides using MALDI-TOF-MS. OBJECTIVE: The aim of this study is to isolate, identify and assess the antimicrobial activity of urinary antimicrobial peptides from healthy normal cycling cows. METHOD: We analyzed the urine sample using diafiltration, ion exchange chromatography, reverse phase high-performance liquid chromatography (RP-HPLC), acid urea polyacrylamide gel electrophoresis (AU-PAGE) coupled with identification through peptide mass fingerprinting (PMF) by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). The in-vitro antimicrobial effects of purified fractions were assessed using radial diffusion assay (RDA) and microtitre broth dilution assay against Gram-positive and Gram-negative bacteria. RESULTS: Proteins corresponding to the peaks were identified using SWISSPROT protein database. This study revealed constitutive expression of ß-Defensin-1 (DEFB1), ß-Defensin-4A (DFB4A), Neutrophil Defensin-1 (DEF1), Neutrophil Defensin-3 (DEF3) in cow urine. The identified peptides are cationic antimicrobial peptides of the defensin family. The purified fractions exhibited antimicrobial effects in radial diffusion assay and MIC values in the range of 2.93-29.3 µM/L. CONCLUSION: This study concludes that cow urine, previously unexplored with regard to antimicrobial peptides, would be a promising source of highly potent AMPs and an effective alternative to the resistant antibiotics.

5.
Int J Pharm ; : 118727, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31626923

RESUMO

This paper provides a method for prediction of weight variability of tablets made in rotary tablet presses as a function of material attributes and processing parameters. The goal was to be able to predict whether or not a formulation is suitable for direct compaction continuous manufacturing using the tablet weight variability as a criterion. The work focused on identifying the significant factors affecting the weight variability in tablets, within the design space studied. A wide range of blends with different powder properties were prepared. It was shown that among powder properties, cohesion, bulk density, and particle size were the most significant and sufficient material attributes to explain tablet weight variability. A response surface model was built and validated with three different blends. The model is not formulation dependent and can be expanded to include other blend properties or processing parameters effects.

6.
Sci Rep ; 9(1): 14486, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31597931

RESUMO

The SrTiO3 thin films were fabricated by pulsed laser deposition. Subsequently ion implantation with 60 keV N ions at two different fluences 1 × 1016 and 5 × 1016 ions/cm2 and followed by annealing was carried out. Thin films were then characterized for electronic structure, morphology and transport properties. X-ray absorption spectroscopy reveals the local distortion of TiO6 octahedra and introduction of oxygen vacancies due to N implantation. The electrical and thermoelectric properties of these films were measured as a function of temperature to understand the conduction and scattering mechanisms. It is observed that the electrical conductivity and Seebeck coefficient (S) of these films are significantly enhanced for higher N ion fluence. The temperature dependent electrical resistivity has been analysed in the temperature range of 80-400 K, using various conduction mechanisms and fitted with band conduction, near neighbour hopping (NNH) and variable range hopping (VRH) models. It is revealed that the band conduction mechanism dominates at high temperature regime and in low temperature regime, there is a crossover between NNH and VRH. The S has been analysed using the relaxation time approximation model and dispersive transport mechanism in the temperature range of 300-400 K. Due to improvement in electrical conductivity and thermopower, the power factor is enhanced to 15 µWm-1 K-2 at 400 K at the higher ion fluence which is in the order of ten times higher as compared to the pristine films. This study suggests that ion beam can be used as an effective technique to selectively alter the electrical transport properties of oxide thermoelectric materials.

7.
Am J Cardiol ; 124(10): 1528-1533, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31521260

RESUMO

The United States is in the kernel of cataclysmic opioid misuse epidemic with over 33,000 deaths per year from both prescription and illegal opioids use. One of the most common pernicious effects of opioids is on the cardiovascular system. The purpose of this analysis was to determine the incidence of opioid overdose associated cardiovascular events and its impact on short-term outcomes. This was a retrospective, observational study which utilized data from the National Inpatient Sample from January 2005 to September 2015 using International Classifications of Disease, Ninth Revision, Clinical Modification diagnosis codes to identify patients with opioid overdose and associated cardiovascular outcomes. Cardiovascular events were mainly divided into the following 3 parts: Ischemic Events (ischemic stroke and myocardial infarction), acute heart failure, and arrhythmias. The primary outcome of this study was incidence of any cardiovascular event. This study analyzed a total of 430,459 patients hospitalized with opioid overdose, out of which 36,837 (8.6%) had at least 1 cardiovascular event. In all the opioid overdose hospitalizations, 13,979 (3.2%) developed ischemic events, 3,074 (0.7%) developed acute heart failure, and 22,444 (5.2%) developed arrhythmia. Opioid overdose patients with new-onset cardiovascular events had higher odds for in-hospital mortality (odds ratio 4.55; 95% confidence interval 4.11 to 5.04, p <0.001) as compared to patients without cardiovascular events in the multivariable-adjusted model. This study group also demonstrated longer length of stay and higher cost of hospitalization associated with opioid overdose and associated cardiovascular outcome. In conclusion, opioid overdose is associated with higher rates of cardiovascular events, particularly ischemic events and cardiac arrhythmias. These adverse events eventually lead to higher mortality rates and more resource utilization.

8.
Food Chem Toxicol ; 134: 110827, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31542433

RESUMO

Lectins are proteins with a high degree of stereospecificity to recognize various sugar structures and form reversible linkages upon interaction with glyco-conjugate complexes. These are abundantly found in plants, animals and many other species and are known to agglutinate various blood groups of erythrocytes. Further, due to the unique carbohydrate recognition property, lectins have been extensively used in many biological functions that make use of protein-carbohydrate recognition like detection, isolation and characterization of glycoconjugates, histochemistry of cells and tissues, tumor cell recognition and many more. In this review, we have summarized the immunomodulatory effects of plant lectins and their effects against diseases, including antimicrobial action. We found that many plant lectins mediate its microbicidal activity by triggering host immune responses that result in the release of several cytokines followed by activation of effector mechanism. Moreover, certain lectins also enhance the phagocytic activity of macrophages during microbial infections. Lectins along with heat killed microbes can act as vaccine to provide long term protection from deadly microbes. Hence, lectin based therapy can be used as a better substitute to fight microbial diseases efficiently in future.

10.
Hepatology ; 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31531989

RESUMO

We read with interest the article by Da et al. (1) on hepatic venous pressure gradient (HVPG) measurement in patients with non-cirrhotic portal hypertension (NCPH). The authors on the basis of HVPG measurement in a cohort of 53 patients had concluded that it is not useful in patients suspected to have NCPH.

11.
Org Lett ; 21(19): 7888-7892, 2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31532213

RESUMO

An example of triorthogonal chemoselectivity is reported here for the first time. In this regard, a series of 43 reactions were performed using tridentate s-triazine as a model. In all of the possible cases, the three substitutions were carried out using different nucleophiles at a temperature compatible with biological systems.

14.
J Card Surg ; 34(8): 714-716, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31376176

RESUMO

The pooled estimate of a recent meta-analysis concluded that rate of reoperation at 1 year was significantly higher in Aortic valve repair (8.82% vs 3.70%) as compared with aortic valve replacement in patients with aortic regurgitation (odds ratio = 2.67, 95% confidence interval [1.08, 3.62], P = .03). We performed a trial sequential analysis using the published data of the meta-analysis and found the evidence is not strong enough for the conclusion.

16.
Sci Rep ; 9(1): 9825, 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31285443

RESUMO

Microbial pattern recognition critically contributes to innate response, both at extracellular and intracellular cytosolic surveillance pathway (CSP) interface. However, the role of pattern recognition by host innate receptors in CSP is poorly understood in Leishmania donovani infection. Here, we have demonstrated that cytosolic targeting of L.donovani DNA (Ld-DNA) inhibits macrophage responsiveness to IFNÉ£, through decreased MHC-II expression and lowered pSTAT1 (Y701) levels, involving host three-prime repair exonuclease-1 (TREX-1). The Ld-DNA potently induced type-1 IFNs, i.e. significant over-production of IFNß through activation of the IRF pathway. Interestingly, knockdown of TRIF or MyD88 expression in macrophages had no effect on cytosolic Ld-DNA transfection-mediated IFN-ß production, indicating involvement of a TLR independent pathway. Contrastingly, Ld-DNA failed to induce IFNß in both TBK-1 and IRF3KO knockout macrophages. Although IFNß was not induced by Ld-DNA in STING- knockout macrophages, STING alone was not enough for the induction. Evidently, besides STING, Ld-DNA recognition for induction of IFNß critically required cytosolic cyclic GMP-AMP synthase (cGAS). Furthermore, the cGAS dependent targeting of Ld-DNA induced IFNß over-production that contributed to antimony resistance in L.donovani infection. We provide the first evidence that enhanced cytosolic sensing of Ld-DNA in infection by antimony resistant (SBR-LD), but not antimony sensitive L.donovani strains (SBS-LD), was critically regulated by host MDRs, multi drug resistant associated protein 1 (MRP 1) and permeability glycoprotein (P-gp) in macrophages. Collectively, our results disclose Ld-DNA as a vital pathogen associated molecular pattern (PAMP) driving host Type-I IFN responses and antimony resistance. The findings may help in future development of policies for novel anti-leishmanial therapeutics.

17.
Angiology ; : 3319719865670, 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31331187
18.
Pediatr Blood Cancer ; 66(11): e27929, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31339233

RESUMO

Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of pathologic immune activation, often associated with genetic defects of lymphocyte cytotoxicity. Though a distinctive constellation of features has been described for HLH, diagnosis remains challenging as patients have diverse presentations associated with a variety of triggers. We propose two concepts to clarify how HLH is diagnosed and treated: within the broader syndrome of HLH, "HLH disease" should be distinguished from "HLH disease mimics" and HLH subtypes should be categorized by specific etiologic associations, not the ambiguous dichotomy of "primary" and "secondary." We provide expert-based advice regarding the diagnosis and initiation of treatment for patients with HLH, rooted in improved understanding of its pathophysiology.

19.
Biosens Bioelectron ; 142: 111526, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31362203

RESUMO

Efficient manipulation of micro biological cells has always been a very important task in healthcare sector for which a Micro Electro Mechanical System (MEMS) based impedance flow cytometry has been proven to be a promising technique. This technique utilise the advantage of dielectrophoresis (DEP) force which is generated by non-uniform electric field in a microfluidic channel using an appropriate external AC supply at certain frequency range. The DEP forces generated in micro-channel depend upon various biological and physical parameters of cell and suspending medium. Apart from that design parameters of microfluidic channel and dimension of electrodes used for generating DEP action also plays major role in micro cell/bead manipulation. This article give remarks on the operating parameters which affects the cell manipulation and interrogates the currently accepted various electrode orientations in microfluidic MEMS flow cytometer technologies for effective manipulation of micro entities like healthy human cells (T-lymphocytes, B- lymphocytes, Monocytes, Leukocytes erythrocytes and human kidney cells HEK293), animal cells (neuroblastoma N115 and sheep red blood cells), cancer cells (MCF-7, MDA-435 and CD34+), yeast cells (saccharomyces cerevisiae, listeria innocua and E. coli) and micro particles (polystyrene beads) based on their dielectric properties using DEP action. Article focuses on the key electrode orientations for generation of non-uniform electric field in microfluidic flow cytometer like tapered electrodes, trapezoidal electrode arrays, Interdigitated electrodes, curved microelectrode and 3D electrode orientations and give remarks on their advantages and limitations. The cell manipulation with current MEMS impedance flow cytometry orientations targeting possibilities of implementation of the lab-on-chip devices has been discussed.

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