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.

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.

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.

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.

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.

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.

Regulation of targeted chemotherapy with cytotoxic lutenizing hormone-releasing hormone analogue by epidermal growth factor.

Targeting chemotherapy selectively to cancers can reduce the toxic side effects. AN-152, a conjugate of doxorubicin and [D-Lys6]-luteinizing hormone-releasing hormone (LH-RH), is more potent against LH-RH receptor-bearing cancers and produces less peripheral toxicity than doxorubicin. Many cancers, e.g., 50% of breast cancers, but few normal tissues express these receptors, providing a selective target for this cytotoxic conjugate. In this study, the effectiveness of AN-152 was heightened by receptor up-regulation. The cytotoxic effect of AN-152 can be regulated by the number of active LH-RH receptors on cancer cells. LH-RH receptor-positive (MCF-7) and -negative (UCI-107) cancer cells were treated with epidermal growth factor (EGF) or the somatostatin analogue, RC-160. EGF and RC-160 have been shown previously to regulate LH-RH receptors through phosphorylation. The effect of receptor regulation, by hormone exposure, on the cytotoxicity of AN-152 and doxorubicin and on the cellular uptake of AN-152, [D-Lys6]LH-RH, or doxorubicin was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and by two-photon laser scanning microscopy. The results demonstrated that the cellular entry of the conjugate was: (a) specific for cancers with LH-RH receptors; (b) up-regulated by EGF; (c) down-regulated by RC-160; and (d) the cytotoxicity of the AN-152 paralleled the efficiency of entry. This study illustrates the potential use of receptor regulation for increasing the efficacy of chemotherapeutic approaches that are directed to cell surface receptors.

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.

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.

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.

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.

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.

Laser Raman investigation of drug-polymer conjugates: sulfathiazole-povidone coprecipitates.

Laser Raman spectroscopy is used for the investigation of the drug-polymer conjugates, sulfathiazole-povidone. Specifically, Raman spectra, both in the lattice vibration and the intramolecular vibration regions, are used to characterize various polymoprhic forms of sulfathiazole. It is found that sulfathiazole exists in two unsolvated forms, untreated sulfathiazole and another form grown from propanol. The crystals grown from ethanol include varying amounts of ethanol depending on the growth condition. The nature of the povidone-sulfathiazole coprecipitates of various compositions are studied. We find no evidence of any new polymorphic form of sulfathiazole in these coprecipitates. The coprecipitates are found to consist of one of the unsolvated forms of sulfathiazole.

Laser Raman investigation of pharmaceutical solids: griseofulvin and its solvates.

Laser Raman spectroscopy is convenient for characterizing griseofulvin solvates and investigating solute-solvent interactions and desolvation. The spectra of both lattice and intramolecular vibrations were monitored. A new solvate of griseofulvin wih bromoform was characterized by Raman spectroscopy. A temperature-dependence study of the solvates of griseofulvin with chloroform, and benzene revealed no phase transformation or chemical change. In the benzene solvate, only weak Van der Waals interactions existed between the solute and solvent. However, in solvates with chloroform and bromoform, a weak hydrogen binding existed between the proton of the solvent and the C = O group of the benzofuran ring in griseofulvin. Examination of desolvation in these solvates revealed that the crystal did not go through any intermediate structure during desolvation. As the solvent molecule escaped, the lattice reverted to the structure of unsolvated griseofulvin.

Three-dimensional laser scanning two-photon fluorescence confocal microscopy of polymer materials using a new, efficient upconverting fluorophore.

Three-dimensional confocal imaging of polymer samples was achieved by the use of two-photon excited fluorescence in both positive and negative contrast modes. The fluorophore was a new and highly efficient two-photon induced upconverter, resulting in improved signal strength at low pumping power. Because of the relatively long wavelength of the excitation source (798 nm from a mode-locked Ti:Sapphire laser), this technique shows a larger penetration depth into the samples than provided by conventional single-photon fluorescence confocal microscopy. Single-photon and two-photon images of the same area of each sample show significant differences. The results suggest the possibility of using two-photon confocal microscopy, in conjunction with highly efficient fluorophores, as a tool to study the surface, interface, and fracture in material science applications.

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.

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.

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.

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

Fabrication of channel waveguides from sol-gel-processed polyvinylpyrrolidone/ SiO(2) composite materials.

Sol-gel-processed composite materials of polyvinylpyrrolidone (PVP) and SiO(2) were studied for optical waveguide applications. PVP is a polymer that can be crosslinked, so it is expected to have high thermal stability after crosslinking. However, thermal crosslinking and thermal decomposition of pure PVP take place around the same temperature, 200 °C, therefore pure PVP had a high optical propagation loss as a result of the absorption of the decomposed molecules after crosslinking. The incorporation of sol-gel-processed SiO(2) prevented the thermal decomposition of PVP and provided remarkably low optical propagation losses. The PVP/SiO(2)composite material also produced thick (>2-µm) crack-free films when the PVP concentration was 50% or higher. An optical propagation loss of 0.2 dB/cm was achieved at 633 nm in the 50% PVP/SiO(2) composite planar waveguide. Several aspects of the thermal stability of the waveguides were evaluated. The slab waveguide was then used for fabrication of channel waveguides with a selective laser-densification technique. This technique used metal lines fabricated with photolithography on the slab waveguide as a light absorbent, and these metal lines were heated by an Ar laser. The resultant channel waveguide had an optical propagation loss of 0.9 dB/ cm at 633 nm. This technique provides lower absorption loss and scattering loss compared with the direct laser-densification technique, which uses UV lasers, and produces narrow waveguides that are difficult to fabricate with a CO(2) laser.