Polymer-coated BiOCl nanosheets for safe and regioselective gastrointestinal X-ray imaging.

Bismuth-based compounds are considered to be the best candidates for computed tomography (CT) imaging of gastrointestinal (GI) tract due to high X-ray absorption. Here, we report the introduction of polymer-coated bismuth oxychloride (BiOCl) nanosheets for highly efficient CT imaging in healthy mice and animal with colitis. We demonstrate simple, low cost and fast aqueous synthesis protocol which provides gram-quantity yield of chemically stable BiOCl nanosheets. The developed contrast gives 2.55-fold better CT enhancement compared to conventional contrast with negligible in vivo toxicity. As a major finding we report a regioselective CT imaging of GI tract by using nanoparticles coated with differentially charged polymers. Coating of nanoparticles with a positively charged polymer leads to their fast accumulation in small intestine, while the coating with negatively charged polymers stimulates prolonged stomach retention. We propose that this effect may be explained by a pH-controlled aggregation of nanoparticles in stomach. This feature may become the basis for advancement in clinical diagnosis of entire GI tract.

Nuclear nanomedicine using Si nanoparticles as safe and effective carriers of 188Re radionuclide for cancer therapy.

Nuclear nanomedicine, with its targeting ability and heavily loading capacity, along with its enhanced retention to avoid rapid clearance as faced with molecular radiopharmaceuticals, provides unique opportunities to treat tumors and metastasis. Despite these promises, this field has seen limited activities, primarily because of a lack of suitable nanocarriers, which are safe, excretable and have favorable pharmacokinetics to efficiently deliver and retain radionuclides in a tumor. Here, we introduce biodegradable laser-synthesized Si nanoparticles having round shape, controllable low-dispersion size, and being free of any toxic impurities, as highly suitable carriers of therapeutic 188Re radionuclide. The conjugation of the polyethylene glycol-coated Si nanoparticles with radioactive 188Re takes merely 1 hour, compared to its half-life of 17 hours. When intravenously administered in a Wistar rat model, the conjugates demonstrate free circulation in the blood stream to reach all organs and target tumors, which is radically in contrast with that of the 188Re salt that mostly accumulates in the thyroid gland. We also show that the nanoparticles ensure excellent retention of 188Re in tumor, not possible with the salt, which enables one to maximize the therapeutic effect, as well as exhibit a complete time-delayed conjugate bioelimination. Finally, our tests on rat survival demonstrate excellent therapeutic effect (72% survival compared to 0% of the control group). Combined with a series of imaging and therapeutic functionalities based on unique intrinsic properties of Si nanoparticles, the proposed biodegradable complex promises a major advancement in nuclear nanomedicine.

Prolonged QT dispersion in Subclinical Hypothyroid Females: A Study in University Teaching Hospital in Central Nepal.

Background QT dispersion is a simple index derived from 12 lead ECG; its prolongation has been shown to be associated with increased arrhythmia risk. Increased cardiovascular risks, particularly occurrence of the malignant arrhythmias are a common finding in patients with subclinical hypothyroidism. This increased arrhythmia risk is found to be higher mainly in patients with TSH level more than 10 milli international unit per liter. Objective To assess QT dispersion among subclinical hypothyroid and euthyroid Nepalese females aged 20-59 years attending general practice out patient department of centrally located University Teaching Hospital from November 2016 to April 2017. Method Forty-three newly detected subclinical hypothyroid females and forty-one euthyroid females were enrolled. Resting electrocardiogram (ECG) was performed. QT dispersion was analyzed from ECG and corrected for heart rate using Framingham correction formula. Independent sample t-test was applied to compare mean QT dispersion between two groups. Pearson correlation test was used to examine the association between QT dispersion and TSH level. Result Mean QT dispersion for sub-clinical hypothyroid group was 75.35 ± 43.82 whereas mean QT dispersion for euthyroid group was 59.51 ± 22.13, with p value 0.041. A weak association between QT dispersion and TSH level was seen with correlation factor of 0.23. Conclusion The result showed prolongation of QT dispersion in sub-clinical hypothyroid group and weak positive correlation between TSH level and QT dispersion suggesting arrhythmia risk in subclinical hypothyroid females.

Management of Organophosphorus Poisoning.

Organophosphorus (OP) compounds are widely used for agriculture, domestic pest-control and chemical warfare. Pesticide self-poisoning accounts for one-sixth to one-eighth of the world's suicides and a third of suicide deaths in rural Asia each year. OP pesticides inhibit cholinesterase enzymes leading to overstimulation of cholinergic receptors. Clinical features depend on the types of receptors stimulated at various sites of the body. The diagnosis of OP poisoning is made on the basis of history of poisoning, smell of pesticides, the characteristic clinical signs and reduced cholinesterase activity. Measurement of plasma cholinesterase is useful for diagnosis of OP poisoning although it may not directly correlate with severity of the poisoning. Atropine remains the main stay of treatment of OP poisoning with clear evidence of benefit if administered effectively. Atropine therapy should be monitored to maintain systolic blood pressure > 80 mmHg, pulse > 80 beats/min and clear chest on auscultation. Oximes reactivate cholinesterase enzymes and help to overcome even the nicotinic effects of OP poisoning. However, evidence for its effectiveness after self-poisoning is weak. Although several newer adjuvant therapies are tried to achieve better outcome, their potential benefits are not yet established.

Nanotherapeutic approach for opiate addiction using DARPP-32 gene silencing in an animal model of opiate addiction.

Opiates act on the dopaminergic system of the brain and perturb 32 kDa dopamine and adenosine 3', 5'-monophosphate-regulated phosphoprotein (DARPP-32) function. The DARPP-32 mediated inhibition of protein phosphatase-1 (PP-1) and modulation of transcriptional factor CREB is critical to the changes in neuronal plasticity that result in behavioral responses during drug abuse. To investigate the role of DARPP-32 mediated signaling on withdrawal behavior in a rat model of opiate addiction, we used intracerebral administration of gold nanorods (GNR) complexed to DARPP-32 siRNA to silence DARPP-32 gene expression and measure its effects on the opiate withdrawal syndrome. We hypothesized that DARPP-32 siRNA will suppress the neurochemical changes underlying the withdrawal syndrome and therefore prevent conditioned place aversion by suppressing or removing the constellation of negative effects associated with withdrawal, during the conditioning procedure. Our results showed that opiate addicted animals treated with GNR-DARPP-32 siRNA nanoplex showed lack of condition place aversive behavior consequent to the downregulation of secondary effectors such as PP-1 and CREB which modify transcriptional gene regulation and consequently neuronal plasticity. Thus, nanotechnology based delivery systems could allow sustained knockdown of DARPP-32 gene expression which could be developed into a therapeutic intervention for treating drug addiction by altering reward and motivational systems and interfere with conditioned responses.

Tracheocele presenting with intermittent dysphonia: a case report.

We report a rare case of tracheocele presenting in an ENT setting. The referral was made on the basis of intermittent dysphonia. The aim of this report is to document the rare condition of tracheocele on the right side and to help raise the level of its awareness among the otolaryngologists. So far approximately thirty cases of this condition have been documented in the literature worldwide. An emphasis is placed on the mode of presentation and the management issues, as early diagnosis is crucial and offers a favorable prognosis. The right sided predilection of the swelling is due to anatomical reason and the cause of recurrent dysphonia is explained.

Fabrication and characterization of gold-polymer nanocomposite plasmonic nanoarrays in a porous alumina template.

A facile, cost-effective, and manufacturable method to produce gold-polymer nanocomposite plasmonic nanorod arrays in high-aspect-ratio nanoporous alumina templates is reported, where the formation of gold nanoparticles and the polymerization of a photosensitive polymer by ultraviolet light are simultaneously performed. Transverse mode coupling within a two-dimensional array of the nanocomposite rods results in a progression of resonant modes in the visible and infrared spectral regions when illuminated at normal incidence, a phenomenon previously observed in nanoarrays of solid gold rods in an alumina template. Finite element full-wave analysis in a three-dimensional computational domain confirms our hypothesis that nanoparticles, arranged in a columnar structure, will show a response similar to that of solid gold rods. These studies demonstrate a new simple method of plasmonic nanoarray fabrication, apparently obviating the need for a cumbersome electrochemical process to grow nanoarrays.

Pralidoxime in organophosphorus poisoning.

INTRODUCTION: Pralidoxime are enzyme reactivator that are known to reactivate the phosphorylated acetylcholinesterase by binding to the organophosphorus molecule. The use of oximes in acute organophosphorus poisoning has been a controversial subjects for over two decades. This study was conducted with the objective to find out the estimation of serum cholinesterase and use of pralidoxime in organophosphorus poisoning. METHODS: A prospective analysis of all organophosphorus poisoning cases presented at the Emergency Department, Tribhuvan University Teaching Hospital for seven months was done. RESULTS: Out of 26 cases about 60% of poisoning cases were monitored for pseudocholinesterase level. About 50% of them had pseudocholinesterase level within normal limit and 20% had less than 10% of normal value. Only 33% cases with pseudocholinesterase level less than 10% were treated with pralidoxime. CONCLUSIONS: The initial dose of Pralidoxime used was 1 gm followed by maintenance dose of 500mg 6 hourly, the doses prescribed were less than WHO recommended doses.

Backward stimulated Bragg scattering in multiphoton active CdTe(x)Se(1-x) quantum dots system.

The backward stimulated Bragg scattering (SBgS) of CdTe(x)Se(1-x) quantum dots in chloroform is investigated at three pump laser wavelengths (532, 816, and 1064 nm) in nanosecond regime. The spectral and temporal structures of the backward stimulated scattering and pump threshold dependence on the concentration are presented in this paper. The energy conversion efficiency from input pump pulse to SBgS pulse was measured to be >or=14%. In addition, the samples exhibit multi- (two-, three-)photon absorption capability over the spectral range we investigated. More importantly, both mechanisms of SBgS and multiphoton absorption provided an enhanced optical limiting performance. The measured nonlinear transmissivity was changed from approximately 0.73 to approximately 0.17 for 532 nm laser pulses and from approximately 0.9 to approximately 0.35 for 816 nm laser pulses when the input pulse energy was changed from 10 to approximately 1500 microJ.

ORMOSIL nanoparticles as a non-viral gene delivery vector for modeling polyglutamine induced brain pathology.

Studies have shown the presence of expanded polyQ containing proteins in brain cells related to Huntington disease (HD) and other poly-glutamine disorders. We report the use of organically modified silica (ORMOSIL) nanoparticles as an efficient non-viral gene carrier in an effort to model brain pathology associated with those disorders induced by expanded polyQ peptides. In experiment 1, plasmids expressing Hemaglutinin-tagged polypeptides with 20 glutamine repeats (Q20) or with extended 127-glutamine repeats (Q127) were complexed with ORMOSIL nanoparticles and injected twice (2 weeks apart) into the lateral ventricle of the mouse brain. Fourteen days post-injection of Q127, immunocytochemistry revealed the presence of the characteristic nuclear and cytoplasmic Q127 aggregates in numerous striatal, septal and neocortical neuronal cells as well as ubiquitin-containing aggregates indicative of the neuronal pathology. The mice receiving Q127 showed a marked increase in the reactive GFAP (+) astrocytes in striatum, septum and brain cortex, further indicating the neurodegenerative changes, accompanied by motor impairments. In experiment 2, plasmids Q20 or Q127 were complexed with ORMOSIL and were injected into the brain lateral ventricle or directly into the striatum of adult rats. In both routes of transfection, Q127 induced the appearance of reactive GFAP (+) astrocytes and activated ED1 antigen expressing microglia. An increase in the size of the lateral ventricle was also observed in rats receiving Q127. In transgenic mouse polyQ models, extensive pathologies occur outside the nervous system and the observed brain pathologies could reflect developmental effects of the toxic polyQ proteins. Our experiments show that the nervous tissue restricted expression of poly Q-extended peptides in adult brain is sufficient to evoke neuropathologies associated with HD and other polyQ disorders. Thus, nanotechnology can be employed to model pathological and behavioral aspects of genetic brain diseases in mice as well as in other species, providing a novel research tool for in vivo testing of single or multi-gene therapies.

Phase-sensitive time-modulated surface plasmon resonance polarimetry for wide dynamic range biosensing.

A novel polarimetry scheme is proposed to improve the performance of phase-sensitive Surface Plasmon Resonance (SPR) biosensors. The scheme uses s-polarized light, not affected by SPR, as a reference beam, while information on the phase of the p-polarized component is obtained from an analysis of phase-polarization state of light of mixed polarization. We utilize temporal modulation of the beam reflected under SPR by a photo-elastic modulator and show that, under certain birefringent geometry, the signals at the 2nd and 3rd harmonics of modulated frequency can provide ultra-sensitive phase-based response to changes of the refractive index (thickness) of thin films on gold. We also show that the proposed configuration significantly improves detection limit compared to conventional intensity-sensitive SPR, yet enables to maintain wide dynamic range of measurements, which is normally difficult with phase-sensitive SPR schemes. Biosensing applications of the proposed scheme are illustrated in a biological model reaction of avidin - biotin binding on gold.

Elasticity-mediated self-organization and colloidal interactions of solid spheres with tangential anchoring in a nematic liquid crystal.

Using laser tweezers, we study colloidal interactions of solid microspheres in the nematic bulk caused by elastic distortions around the particles with tangential surface anchoring. The interactions overcome the Brownian motion when the interparticle separation r-->p is less than 3 particle diameters. The particles attract when the angle theta between r-->p and the uniform far-field director n0 is between 0 degrees and approximately 70 degrees and repel when 75 degrees

Gold nanoshells on polystyrene cores for control of surface plasmon resonance.

A method is presented for synthesizing core-shell structures consisting of monodisperse polystyrene latex nanospheres as cores and gold nanoparticles as shells. Use of polystyrene spheres as the core in these structures is advantageous because they are readily available commercially in a wide range of sizes, and with dyes or other molecules doped into them. Gold nanoparticles, ranging in size from 1 to 20 nm, are prepared by reduction of a gold precursor with sodium citrate or tetrakis(hydroxymethyl)phosphonium chloride (THPC). Carboxylate-terminated polystyrene spheres are functionalized with 2-aminoethanethiol hydrochloride (AET), which forms a peptide bond with carboxylic acid groups on their surface, resulting in a thiol-terminated surface. Gold nanoparticles then bind to the thiol groups to provide up to about 50% coverage of the surface. These nanoparticles serve as seeds for growth of a continuous gold shell by reduction of additional gold precursor. The shell thickness and roughness can be controlled by the size of the nanoparticle seeds as well as by the process of their growth into a continuous shell. By variation of the relative sizes of the latex core and the thickness of the gold overlayer, the plasmon resonance of the nanoshell can be tuned to specific wavelengths across the visible and infrared range of the electromagnetic spectrum, for applications ranging from the construction of photonic crystals to biophotonics. The position and width of the plasmon resonance extinction peak are well-predicted by extended Mie scattering theory.

Chemically fabricated magnetic quantum dots of InP:Mn.

Quantum dots of InP:Mn are chemically prepared by following hot colloidal nanochemistry with starting precursors that obviate the need for external surfactant. These quantum dots are uniform spheres with 3-nm diameters; they are crystalline, photoluminescent, and magnetic. The crystallographic and optical properties are similar to those of undoped InP nanocrystallites, while the magnetism is consistent with the ferromagnetic response observed in a class of diluted magnetic semiconductors. Because of the ultrafine sizes, the sample shows superparamagnetic behavior, whereas ferromagnetic hysteresis loops are clearly seen below the blocking temperature. Structural characterization and analysis confirm that the magnetism in these quantum dots is not due to segregated binary MnP or MnO phases and that they truly represent a homogeneous dilute magnetic semiconductor.

Polycarboxylic acid nanoparticles for ophthalmic drug delivery: an ex vivo evaluation with human cornea.

In ophthalmic drug delivery, a major problem is retaining an adequate concentration of a therapeutic agent in the pre-corneal area. Polycarboxylic acid carriers such as polyacrylic acid and polyitaconic acid in sub-colloidal, nanoparticulate hydrogel form have a strong potential for sustained release of a drug in ocular delivery. Formulations have been prepared of brimonidine loaded in polycarboxylic (polyacrylic and polyitaconic) acid nanoparticles for potential ophthalmic delivery. These particles were prepared by a reverse micro-emulsion polymerization technique with sizes in the range of 50 nm. The loading efficiencies of the drug brimonidine in the particles were shown to be between 80-85% for polyacrylic acid nanoparticles and between 65-70% for polyitaconic nanoparticles. The loading efficiency was also found to be pH dependent. In a preliminary biocompatibility test, human corneal epithelial cells incubated with polyacrylic acid nanoparticles were found to retain their viability, whereas polyitaconic acid nanoparticles were found to be toxic. Two-photon laser scanning microscopic studies of the fluorescently labelled polyacrylic acid nanoparticles and human cornea shows that they are adhesive on the corneal surface. The polyacrylic acid nanoparticles demonstrated a controlled release of the opthalmological drug (Brimonidine) through the human cornea as compared to that of the commercial formulation, Alphagan.

Measurement of optical trapping forces by use of the two-photon-excited fluorescence of microspheres.

A novel technique for the calibration of laser trapping systems that utilizes two-photon-excited fluorescence of commercial dye-stained microspheres has been demonstrated. The trapping forces as well as the trapping efficiency have been measured for various liquid environments and trapping depths. The trapping efficiency in water was found to decrease with an increase of trapping depths because of the enlargement of the trapping beam waist caused by aberrations of the optical system.

Brimonidine formulation in polyacrylic acid nanoparticles for ophthalmic delivery.

In ocular drug delivery, a major problem is providing an adequate concentration of a therapeutic agent in the precorneal area. Mucoadhesive carriers such as polyacrylic acid in sub-colloidal, nanoparticulate form, have a strong potential for ophthalmic drug delivery. A formulation of brimonidine loaded in polyacrylic acid nanoparticles has been prepared for potential delivery in ophthalmic therapy. The particles were prepared by a reverse microemulsion polymerization technique and their sizes were in the range of 50 nm. In a preliminary biocompatibility test, Caco-2 cells (human primary colonic tumour adenocarcinoma) and human corneal epithelial cells incubated with polyacrylic acid nanoparticles were found to retain their viability over varying times. The loading efficiency of the drug brimonidine in the particles was shown to be between 80-85% and pH dependent. The bioadhesive polyacrylic hydrogel nanoparticles, used in the present study, exhibited superior loading properties for brimonidine, and the formulation was stable for more than 5 weeks. When the drug-loaded nanoparticles were dispersed in a phosphate buffer saline (pH = 7.4), the drug was slowly released over several hours. Two-photon laser scanning microscopic studies of dye-conjugated polyacrylic acid nanoparticles demonstrated the accumulation of the particles on the surface and intercellular spaces of Caco-2 cells.

Studies on the mechanism of action of a targeted chemotherapeutic drug in living cancer cells by two photon laser scanning microspectrofluorometry.

In this study, we present a spectroscopic study of the entry pattern of a chemotherapeutic drug (AN-152) and its carrier hormone ([D-Lys(6)]LH-RH) into living cancer cells, with the help of our two-photon probes and a home-built localized microspectrofluorometer coupled with two photon laser scanning microscope (TPLSM). Due to the inherent localization ability of TPLSM, we were able to identify the drug and carrier location in different compartments of the cancer cells in vitro. The apparent doxorubicin-assisted nucleic accumulation of AN-152 suggests a possible nuclear action of the drug on cell proliferation.

High-density optical data storage with one-photon and two-photon near-field fluorescence microscopy.

A spatially localized photochemical reaction induced by near-field femtosecond laser pulses is demonstrated on a nanometer scale and used for high-density optical data storage. Recorded domains down to 120 and 70 nm are obtained with one-photon and two-photon excitation, respectively. It is shown that the local-field confinement that is due to the quadratic dependence of two-photon excitation on light intensity has the potential to increase the near-field optical storage density.

Nanoscopic study of second-harmonic generation in organic crystals with collection-mode near-field scanning optical microscopy.

Collection-mode near-field scanning optical microscopy (NSOM) is used to map nanoscopic second-harmonic generation (SHG) in N -(4-nitrophenyl)- (L) -prolinol crystals. A spatial resolution of 98 nm is achieved. Near-field polarization-dependent SHG measurement is performed, and a local effective SHG susceptibility of 224+/-18 pm/V is obtained.