Publications by authors named "Ratnakar S"

Background: Recent evidence suggests that oral squamous cell carcinoma (OSCC) patients who exhibit the immunohistochemical expression of immune checkpoint protein programmed cell death ligand 1 (PD-L1) are more likely to have a poor clinical outcome and may serve as an independent prognostic marker.

Aims And Objectives: This study aimed to assess the immunohistochemical expression of immune checkpoint protein PD-L1 in OSCC and its clinicopathological correlation.

Materials And Methods: OSCC cases were included in the study.

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A Mn(II)-based zinc-sensitive MRI contrast agent, MnPyC3A-BPEN, was prepared, characterized, and applied in imaging experiments to detect glucose-stimulated zinc secretion (GSZS) from the mouse pancreas and prostate . Thermodynamic and kinetic stability tests showed that MnPyC3A-BPEN has superior kinetic inertness compared to GdDTPA, is less susceptible to transmetalation in the presence of excess Zn ions, and less susceptible to transchelation by albumin. In comparison with other gadolinium-based zinc sensors bearing a single zinc binding moiety, MnPyC3A-BPEN appears to be a reliable alternative for imaging β-cell function in the pancreas and glucose-stimulated zinc secretion from the prostate.

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Article Synopsis
  • Paramagnetic chemical exchange saturation transfer (paraCEST) agents are ideal for imaging tissue pH due to their sensitivity to changes in pH through chemical exchange.
  • The new pH-sensitive paraCEST agent developed lacks an inner-sphere water molecule and instead uses a Yb-bound -OH group, providing a distinct CEST peak that correlates with varying pH levels.
  • Initial rodent studies indicate that the Gd(1) complex has a prolonged presence in the bloodstream but is eventually cleared slowly through the kidneys.
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EuDOTA-glycine derivatives have been explored as alternatives to typical gadolinium-containing complexes for MRI agents used in diagnostic imaging. Different imaging modalities can be accessed ( or PARACEST) dependent on the oxidation state of the europium ion. Throughout the past 30 years, there have been significant manipulations and additions made to the DOTA scaffold; yet, characterizations related to electrochemistry and structure determined through XRD analysis have not been fully analyzed.

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Background: Masonry workers engaged in occupational work-activities have high risk of shoulder injury that often develops to functional loss and disability. Rehabilitative exercises (REs) have potential for slowing this development.

Objective: The objective is to study the effects of three selected REs on integrated electromyography activations of the external rotator muscles and trapezius muscles of masonry workers.

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The Eu redox couple provides a convenient design platform for responsive O sensors for magnetic resonance imaging (MRI). Specifically the Eu ion provides contrast enhancement under hypoxic conditions in tissues, whereas, under normoxia, the Eu ion can produce contrast from chemical exchange saturation transfer in MRI. The oxidative stability of the Eu redox couple for a series of tetraaza macrocyclic complexes was investigated in this work using cyclic voltammetry.

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The Eu(II) complex of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) tetra(glycinate) has a higher reduction potential than most Eu(II) chelates reported to date. The reduced Eu(II) form acts as an efficient water proton T1 relaxation reagent, while the Eu(III) form acts as a water-based chemical exchange saturation transfer (CEST) agent. The complex has extremely fast water exchange rate.

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Purpose: The water molecule exchange rates in a series of DyDOTA-(amide)X chelates were fine-tuned to maximize the effects of T2-exchange line broadening and improve T2 contrast.

Methods: Four DyDOTA-(amide)X chelates having a variable number of glycinate side-arms were prepared and characterized as T2-exchange agents. The nonexchanging DyTETA chelate was also used to measure the bulk water T2 reduction due solely to T2*.

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A novel approach for the design of responsive paramagnetic chemical exchange saturation transfer (PARACEST) magnetic resonance imaging (MRI) agents has been developed where the signal is "turned on" by altering the longitudinal relaxation time (T1) of bulk water protons. To demonstrate this approach, a model Eu(DOTA-tetraamide) complex (DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) containing two nitroxide free radical units was synthesized. The nitroxide groups substantially shortened the T1 of the bulk water protons which, in turn, resulted in quenching of the CEST signal.

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The free radical 2,2-diphenyl-1-pycrylhydrazyl (DPPH) was tested as a polarising agent for fast dissolution dynamic nuclear polarisation (DNP) NMR spectroscopy. DPPH was found to be reasonably soluble in sulfolane and the optimum concentration for DNP is 20-40 mM depending upon whether short polarisation times or the maximum signal intensity is needed. W-band ESR measurements revealed that the ESR linewidth D of DPPH is intermediate between that of BDPA and 4-oxo-TEMPO.

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PARACEST redox sensors containing the NAD(+)/NADH mimic N-methylquinolinium moiety as a redox-active functional group have been designed and synthesized. The Eu(3+) complex with two quinolinium moieties was nearly completely CEST-silent in the oxidized form but was "turned on" upon reduction with β-NADH. The CEST effect of the Eu(3+) complex containing only one quinolinium group was much less redox-responsive but showed an unexpected sensitivity to pH in the physiologically relevant pH range.

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Both isotopes of silver, (107)Ag and (109)Ag, were simultaneously polarized by dynamic nuclear polarization (DNP), thus allowing large signal enhancements and the NMR characterization of Ag complexes in the millimolar concentration range. Since both isotopes have long relaxation times T(1), the hyperpolarized NMR signal of one isotope could still be observed even after the magnetization of the other isotope had been destroyed by radio-frequency pulses.

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Ln(S-THP)(3+) complexes are paramagnetic chemical exchange saturation transfer (PARACEST) agents for magnetic resonance imaging (MRI; S-THP = (1S,4S,7S,10S)-1,4,7,10-tetrakis(2-hydroxypropyl)-1,4,7,10-tetraazacyclododecane, Ln(III) = Ce(III), Eu(III), Yb(III)). CEST spectra at 11.7 T show that the PARACEST effect of these complexes is enhanced at neutral pH in buffered solutions containing 100 mM NaCl upon the addition of 1-2 equiv of diethylphosphate (DEP).

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Chemical exchange-dependent saturation transfer and paramagnetic chemical exchange-dependent saturation transfer are agent-mediated contrast mechanisms that depend on saturating spins at the resonant frequency of the exchangeable protons on the agent, thereby indirectly saturating the bulk water. In general, longer saturating pulses produce stronger chemical and paramagnetic exchange-dependent saturation transfer effects, with returns diminishing for pulses longer than T1. This could make imaging slow, so one approach to chemical exchange-dependent saturation transfer imaging has been to follow a long, frequency-selective saturation period by a fast imaging method.

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Caregiving to a family member with advanced cancer can be stressful. Stress leads to psychological changes, oxidative stress and increased glomerular permeability to proteins. To find out their association with stress, we assessed anxiety and depression by the hospital anxiety and depression scale (HADS), urinary malondialdehyde:creatinine ratio (UMDA:Cr), urinary protein:creatinine ratio (UP:Cr) and SDS-polyacrylamide gel electrophoresis (SDS-PAGE) profile of urinary proteins in 31 family caregivers of advanced cancer patients and 31 matched controls.

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The chemical exchange saturation transfer (CEST) efficiency for a series Eu3+-based tetraamide complexes bearing p-substituents on a single coordinating pendant arm is highly sensitive to water exchange rates. The CEST effect increases in the order Me < MeO < F approximately CO2tBu < CN < H. These results show that CEST contrast can be modulated by changes in electron density at a single ligating atom, and this forms the basis of creating imaging agents that respond to chemical oxidation and reduction.

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