Presence Of Theophylline Research Articles

An electrochemical sensor based on a modified glassy carbon electrode for detection of epinephrine in the presence of theophylline.

Neurotransmitters are chemical messengers that enhance and balance signals between cells and target cells in the body. They are vital to the body's ability to function. Epinephrine is one of the most essential catecholamine neurotransmitters with an important biological and pharmacological role in the mammalian central nervous system. Therefore, it is very important to develop sensitive, simple, and fast methods for the determination of this compound. In the present work, a glassy carbon electrode (GCE) modified with the cerium oxide-zinc oxide (CeO2-ZnO) nanocomposite (CeO2-ZnO/GCE) was developed for the sensitive and quick detection of epinephrine. The CeO2-ZnO nanocomposite was prepared by hydrothermal method. Electrochemical methods such as voltammetry and chronoamperometry techniques were used to investigate the performance of the developed sensor. The resulting CeO2-ZnO/GCE showed a remarkable response towards the determination of epinephrine. The electrochemical sensor demonstrated a wide dynamic linear range from 0.1 to 900.0 μM for analysis of epinephrine. The LOD equalled 0.03 μM for epinephrine. In addition, the electrochemical sensor had good feasibility for concurrent detection of epinephrine and theophylline. Furthermore, experimental outputs indicated that the oxidation peaks of epinephrine and theophylline were separated by a 685 mV difference between the two peaks in PBS at a pH of 7.0. Also, an electrochemical sensor has been employed to analyse epinephrine in real samples (urine and epinephrine Injection). The good and acceptable analytical performance of the developed sensor can provide a promising tool for the analysis of epinephrine in real samples.

Electrochemical investigation of an anticancer drug 5-Fluorouracil in the presence of Theophylline using low-cost and disposable poly(GLY) modified pencil graphite electrode

Herein this study, a facile, efficient and disposable electrochemical sensor has been prepared by electropolymerization of glycine (poly(GLY)) on the surface of pencil graphite electrode (PGE). The surface topology of the equipped poly(GLY) modified pencil graphite electrode (poly(GLY)/PGE) and bare pencil graphite electrode (BPGE) has been characterized by the scanning electron microscopy (SEM) combined with energy dispersive x-ray analysis (EDX) and charge transfer behaviour was measured by electron impedance spectroscopy (EIS) method. The voltammetric behaviour of anticancer, 5-fluorouracil (5-FU) in the presence of theophylline (THP) has been carried out in 0.1 M phosphate buffer solution (PBS) of physiological pH 7.0 using different techniques such as cyclic voltammetry (CV), linear sweep voltammetry (LSV) and differential pulse voltammetry (DPV). The proposed poly(GLY)/PGE shows augmented peak current for 5-FU at lower potential side over the BPGE due to the electrocatalytic behaviour of modifier layers wrapped on the electrode surface. The kinetic behaviour of 5-FU at modified electrode surface was studied by varying different parameters such as pH, scan rate and concentration study in 0.1 M PBS used as a supporting electrolyte. The limit of detection (LOD) for 5-FU was attained using DPV method with different concentrations (1.0–13.0 μM) and it was found to be 0.012 μM. The possible electrochemical reaction of 5-FU was proposed and it was incorporated by two electrons and two protons mechanism at modified electrode surface. The voltammetric response of poly(GLY)/PGE towards the determination of 5-FU was unaffected in the presence of some excipients in addition to the remarkable stability and reproducibility. The applicability of the proposed sensor has been performed by real sample investigation of 5-FU with a substantial percentage of recovery results in all optimized conditions.

A novel fluorescent aptasensor for the detection of theophylline based on cryonase-driven signal amplification strategy.

In the study, we have developed an expedient and efficient method for the detection of theophylline based on the amplification of the signal intensity of fluorescence based on oxidized single-walled carbon nanohorns (oxSWCNHs)/cryonase. When theophylline was not present in the system, oxSWCNHs can adequately adsorb nucleic acid probes labeled by carboxyfluorescein (FAM). In the presence of theophylline, the nucleic acid probe forms the tertiary probe-theophylline complex, which detaches from the surface of the oxSWCNHs. Then, upon reaction with cryonase, the complex can release the FAM and theophylline into the next cycle. The fluorescence signal of the system exhibits a 1:N magnification, enabling quantitative detection of theophylline. The linear range was 30-150 ng/mL, and the limit of detection (LOD) was 6.04 ng/mL. At the same time, it can also be used to detect theophylline in mouse serum.

Inhibition of uterine contractility by guanine-based purines in non-pregnant rats.

Growing evidence pointed out that guanine-based purines are able to modulate smooth muscle contractile activity of blood vessels and gastrointestinal tract. Since, so far, possible guanine-based purine modulation of uterine musculature is unknown, the aim of the present study was to investigate in vitro, using organ bath technique, guanosine and guanine effects on spontaneous uterine contraction, and uterine contraction induced by K+-depolarization and oxytocin in a non-pregnant rat. Guanosine, but not guanine, reduced the amplitude of spontaneous contraction of the uterine muscle in a dose-dependent manner. The inhibitory response was antagonized by S-(4-nitrobenzyl)-6-thioinosine (NBTI), a membrane nucleoside transporter inhibitor, but persisted in the presence of theophylline, a nonselective adenosine receptor antagonist, or propanolol, β1/β2 adrenoreceptor antagonist or blockers of a nitrergic pathway. In addition, potassium channel blockers did not influence guanosine-induced effects. Guanosine was able to inhibit the external calcium (Ca2+) influx-induced contraction, but it did not affect the contraction induced by high-KCl solution, indicating that guanosine does not interact with L-type voltage-gated calcium channel. Guanosine prevented/reduced uterine contractions induced by oxytocin, even in the absence of external calcium. In conclusion, guanosine is able to reduce both spontaneous and oxytocin-induced contractions of rat myometrium, likely subsequently to its intracellular intake. The blockade of extracellular Ca2+ influx and reduction of Ca2+ release from the intracellular store are the mechanisms involved in the guanosine-induced tocolytic effects.

Reactive oxygen species-dependent upregulation of death receptor, tumor necrosis factor receptor 1, is responsible for theophylline-mediated cytotoxicity in MDA-MB-231 breast cancer cells.

Theophylline, a methylxanthine drug, has been used as a therapy for respiratory diseases. Recently, it has also been shown to have a potential in treating different cancers. Also, it has shown promising results in clinical trials for AML in combination therapy. Subsequently, studies have shown theophylline to kill breast cancer cells but not normal breast cells. Therefore, in this study, we have explored the molecular mechanism underlying the cytotoxic effect of theophylline on breast cancer cells. Theophylline-treated cancer cells were analyzed for the transcript and protein expression of candidate apoptotic genes such as TNFR1, caspase-8, -9, -3 using qPCR and immunoblotting, respectively. Cell viability and apoptosis was measured in the presence or absence of TNFR1 inhibitor, R7050, using AO/EtBr staining and MTT assay, respectively. Similarly, oxidative stress was studied by analyzing ROS in the presence or absence of ROS inhibitor, NAC, using DCFDA assay. Theophylline caused reduced cell viability in cancer but not normal cells. Theophylline-treated breast cancer cells showed increased expression of death receptor, TNFR1, along with elevated levels of active caspase-8, -9 and -3. Inhibition of TNFR1 reduced caspase-dependent apoptosis even in the presence of theophylline. Theophylline further caused increased ROS generation, inhibition of which resulted in reduced TNFR1-mediated apoptosis. Theophylline also increased cathepsin activity, which was reduced on exposure of cells to TNFR1 inhibitor, R7050. We conclude that ROS-mediated activation of TNFR1 is responsible for caspase-3 and cathepsin-dependent cell death in breast cancer cells on exposure to theophylline.

Electrochemical sensing platform based on modified graphite screen-printed electrode to determine isoproterenol in the presence of theophylline and acetaminophen

Electrochemical sensing platform based on modified graphite screen-printed electrode to determine isoproterenol in the presence of theophylline and acetaminophen

Complexing deoxyribozymes with RNA aptamers for detection of the small molecule theophylline

Biointegrative information processing systems offer a great advantage to autonomous biodevices, as their capacity for biological computation provides the ability to sense the state of more complex environments and better integrate with downstream biological regulation systems. Deoxyribozymes (DNAzymes) and aptamers are of interest to such computational biosensing systems due to the enzymatic properties of DNAzymes and the ligand-inducible conformational structures of aptamers. Herein, we describe a novel method for providing ligand-responsive allosteric control to a DNAzyme using an RNA aptamer. We designed a NOT-logic-compliant E6 DNAzyme to be complementary to an RNA aptamer targeting theophylline, such that the aptamer competitively interacted with either theophylline or the DNAzyme, and disabled the DNAzyme only when theophylline concentration was below a given threshold. Out of our seven designed “complexing aptazymes,” three demonstrated effective theophylline-responsive allosteric regulation (2.84 ± 3.75%, 4.97 ± 2.92%, and 8.91 ± 4.19% activity in the absence of theophylline; 46.29 ± 3.36%, 50.70 ± 10.15%, and 61.26 ± 6.18% activity in the presence of theophylline). Moreover, the same three complexing aptazymes also demonstrated the ability to semi-quantitatively determine the concentration of theophylline present in solution, successfully discriminating between therapeutically ineffective (<20 μM), safe (20–100 μM), and toxic (>100 μM) theophylline concentrations. Our method of using an RNA aptamer for ligand-responsive allosteric control of a DNAzyme expands the way aptamers can be configured for biosensing, and suggests a pathway for embedding DNAzymes to provide enhanced information processing and control of biological systems.

Rapid and Sensitive Quantification of Isoproterenol in the Presence of Theophylline by CuO Nanoflowers Modified Electrochemical Sensor

Isoproterenol is an important catecholamine-based drug that is widely used in the treatment of heart disease. The present paper introduced one of the new modifications for the surfaces of glassy carbon electrodes (GCEs) using the CuO nanoflowers (CuO NFs) for determination of isoproterenol. Electrochemical properties of the CuO NFs/GCE for detecting isoproterenol were tested using the cyclic voltammetry (CV), chronoamperometry (CHA) as well as differential pulse voltammetry (DPV). Electrochemical studies demonstrated an efficient isoproterenol oxidation, with enhanced peak current from 2.9 µA to about 10.0 µA (3.4% increase) and decreased peak potential from 500 mV to about 300 mV. The linear response for the determination of isoproterenol was obtained in ranges for concentrations between 0.3 and 450.0 μM under the most proper conditions and the limit of detection (LOD) equaled 0.09 μM. Also, the modified electrode is utilized for simultaneously determining isoproterenol and theophylline using DPV. The proposed CuO NFs/GCE sensor was effectively employed for the isoproterenol and theophylline detection in the isoproterenol ampoule and urine samples.

A malachite green light-up aptasensor for the detection of theophylline

Biosensors are of interest for the quantitative detection of small molecules (metabolites, drugs and contaminants for instance). To this end, fluorescence is a widely used technique that is easily associated to aptamers. Light-up aptamers constitute a particular class of oligonucleotides that, specifically induce fluorescence emission when binding to cognate fluorogenic ligands such as malachite green (MG). We engineered a dual aptasensor for theophylline (Th) based on the combination of switching hairpin aptamers specific for MG on the one hand and for Th on the other hand, hence their names: malaswitch (Msw) and theoswitch (Thsw). The two aptaswitches form a loop-loop or kissing Msw-Thsw complex only in the presence of theophylline, allowing binding of MG, subsequently generating a fluorescent signal. The combination of the best Msw and Thsw variants, MswG12 and Thsw19.1, results in a 20-fold fluorescence enhancement of MG at saturating theophylline concentration. This aptasensor discriminates between theophylline and its analogues caffeine and theobromine. Kissing aptaswitches derived from light-up aptamers constitute a novel sensing device.

Electro-catalytic amplified sensor for determination of N-acetylcysteine in the presence of theophylline confirmed by experimental coupled theoretical investigation

The 1,l/-bis(2-phenylethan-1-ol)ferrocene, 1-butyl-3-methylimidazolium hexafluoro phosphate (BMPF6) and NiO-SWCNTs were used to modify carbon paste electrode (BPOFc/BMPF6/NiO-SWCNTs/CPE), which could act as an electro-catalytic tool for the analysis of N-acetylcysteine in this work. The BPOFc/BMPF6/NiO-SWCNTs/CPE with high electrical conductivity showed two completely separate signals with oxidation potentials of 432 and 970 mV for the first time that is sufficient for the determination of N-acetylcysteine in the presence of theophylline. The BPOFc/BMPF6/NiO-SWCNTs/CPE showed linear dynamic ranges of 0.02–300.0 μM and 1.0–350.0 μM with the detection limit of ~ 8.0 nM and 0.6 μM for the measurement of N-acetylcysteine and theophylline, respectively. In the second part, understanding the nature of interaction, quantum conductance modulation, electronic properties, charge density, and adsorption behavior of N-acetylcysteine on NiO–SWCNTs surface from first-principle studies through the use of theoretical investigation is vital for designing high-performance sensor materials. The N-acetylcysteine molecule was chemisorbed on the NiO–SWCNTs surface by suitable adsorption energies (− 1.102 to − 5.042 eV) and reasonable charge transfer between N-acetylcysteine and NiO–SWCNTs.

Determination of methylxanthines in tea samples by HPLC method

Abstract Methylxanthines such as caffeine, theophylline, theobromine are significant and widespread psychoactive substances. We developed the isocratic method with optimum composition of the mobile phase 90 % water: 10 % acetonitrile and confirmed repeatability of retention times and peak areas. The developed HPLC method was applied to determine the content of methylxanthines in selected types of black and green teas available on the market. Of the black teas (tea bags), the highest concentration of theobromine was found in Ceylon tea (18.98 mg.L−1). The highest concentration of caffeine was in a cup of Earl Gray tea (254.09 mg.L−1). Among loose black teas, the highest content of both theobromine and caffeine was found in Pu Erh Superior tea, where the theobromine content was 24.62 mg.L−1 and the caffeine content was 520.67 mg.L−1. Of green powder teas, highest caffeine content (306.46 mg.L−1) was in Shizuoka Matcha Premium and the highest content of theobromine (8.45 mg.L−1) was found in GABA Midori. From the loose green tea, the highest concentration of theobromine (12.85 mg.L−1) was in Lung Ching West Lake. The highest caffeine content (484.85 mg.L−1) was in Gyokuro Shizuoka Premium Tea. In both types of teas the amount of theobromine and caffeine was quantified, but the presence of theophylline was not proven. Data on contents of these metabolites in tea products are highly informative for consumers.

Engineering Riboswitches in Vivo Using Dual Genetic Selection and Fluorescence-Activated Cell Sorting.

Riboswitches, noncoding RNAs that bind a small molecule effector to control gene expression at the level of transcription or translation, are uniquely suited to meet challenges in synthetic biology. To expand the limited set of existing riboswitches, we developed a riboswitch discovery platform that couples dual genetic selection and fluorescence-activated cell sorting to identify novel riboswitches from a 108 random-sequence library in which the aptamer domain of the ThiM#2 riboswitch was replaced with an N40 sequence. In a proof-of-principle validation, we identified novel riboswitches for the small molecule theophylline. Our best riboswitch (Hit 3-5) displays 2.3-fold activation of downstream gene expression in the presence of theophylline. Random mutagenesis of Hit 3-5, coupled with selections and screens, afforded improved riboswitches displaying nearly 3-fold activation. To the best of our knowledge, this is the first report of in vivo directed evolution of an aptamer domain to generate a functional riboswitch.

INHIBITORY EFFECT OF ETHANOLIC EXTRACT OF ERIOBOTRYA JAPONICA LEAVES PRE-INCUBATED WITH THEOPHYLLINE AND ASPIRIN ON ISOLATED GUINEA PIG TRACHEAL

Objectives: The objectives of the study were to examine the inhibitory effect of ethanol extract of Eriobotrya japonica leaves (EEEJL) pre-incubated with theophylline and aspirin on isolated guinea pig tracheal chains against acetylcholine (ACh)-induced contraction.Methods: The effect of EEEJL (1-8 mg/Ml) on the isolated tracheal strips was tested in vitro. Furthermore, the mechanism of relaxant effects of EEEJL was evaluated in the presence of theophylline and aspirin.Results: The contractile response evoked by Ach (1.25 × 10−3 M) was decreased by EEEJL (effective concentration50 = 1.36 mg/mL) and has no significant difference of relaxant effect to that of EEEJL pre-incubated with theophylline and aspirin (p&gt;0.05).Conclusion: The EEEJL decreased the ACh-induced contraction through the inhibition of PDE and the protective effect on prostaglandin E2.

Electrochemical Platform Based on Synergic Effect of Fe3O4/SWCNTs and 1-ethyl-3-methyl Imidazolium Chloride as Sensor for Determination of Xanthine and Theophylline in Food Samples

Fe3O4 decorated single wall carbon nanotubes (Fe3O4/SWCNTs) composite and1-ethyl-3-methyl imidazolium chloride (1E3MICl) were used for modification of carbon paste electrode (CPE) and fabricated sensor applied to the sensitive and convenient determination of xanthine (Xt). The carbon paste electrode amplified with 1E3MICl and Fe3O4/SWCNTs (CPE/1E3MICl/Fe3O4/SWCNTs) exhibit an anodic peak for Xt at potential ∼ 830 mV that is about 135 mV less positive than detected potential for Xt at an unmodified CPE in the similar condition. In addition, the CPE/1E3MICl/ Fe3O4/SWCNTs exhibit a potential ability for analysis of Xt in the presence of theophylline (Tp) with the separated potential 280 mV. The CPE/1E3MICl/ Fe3O4/SWCNTs was used for determination of Xt and Tp in the concentration ranges of 4.0 nM–300.0 μM and 0.1–300.0 μM, respectively. The CPE/1E3MICl/Fe3O4/SWCNTs was used as a high performance sensor with good detection limit for determination of Xt in food samples such as fish meat, tea and soft drinks.

Colorimetric theophylline aggregation assay using an RNA aptamer and non-crosslinking gold nanoparticles.

The authors are presenting a rapid method for the determination of theophylline using unique non-crosslinking gold nanoparticle (AuNP) aggregation. An RNA aptamer against theophylline is firstly split into two RNA fragments which then interact with bare AuNPs. The two RNA probes cause an enhancement of the salt tolerance of AuNPs. However, in the presence of theophylline, the RNA probes form a complex with theophylline so that less RNA probes are available to protect the AuNPs from salt-induced aggregation. Theophylline induced aggregation of AuNPs is accompanied by a color change from red to blue. The color change can be detected visually and via UV-vis absorptiometry by ratioing the absorbances at 650 and 520nm. The ratio increases linearly in the 0.1 to 20μM theophylline concentration range, with a 67nM limit of detection. The method is highly sensitive and selective. Graphical abstract Single-stranded split RNA aptamers (R1 and R2) protect gold nanoparticles (AuNPs) from salt-induced non-crosslinking aggregation. After recognition of theophylline by the RNA probe, the unprotected AuNPs aggregate and undergo a color change from red to blue, and this is used to quantify the theophylline concentration.

Controlling Bdellovibrio bacteriovorus Gene Expression and Predation Using Synthetic Riboswitches.

Bdellovibrio bacteriovorus is a predatory bacterium that feeds on Gram-negative bacteria including a wide range of pathogens and thus has potential applications as a biocontrol agent. Owing to its unique life cycle, however, there are limited tools that enable genetic manipulation of B.bacteriovorus. This work describes our first steps toward engineering the predatory bacterium for practical applications by developing basic genetic parts to control gene expression. Specifically, we evaluated four robust promoters that are active during the attack phase of B.bacteriovorus. Subsequently, we tested several synthetic riboswitches that have been reported to function in Escherichia coli, and identified theophylline-activated riboswitches that function in B.bacteriovorus. Finally, we inserted the riboswitch into the bacterial chromosome to regulate expression of the flagellar sigma factor fliA, which was previously predicted to be essential for predation, and observed that the engineered strain shows a faster predation kinetics in the presence of theophylline.

Molecular Mobility of an Amorphous Chiral Pharmaceutical Compound: Impact of Chirality and Chemical Purity

A dielectric relaxation spectroscopy (DRS) study was performed to investigate the molecular mobility of amorphous chiral diprophylline (DPL). For this purpose, both racemic DPL and a single enantiomer of DPL were considered. After fast cooling from the melt at very low temperature (-140 °C), progressive heating below and above the glass transition (Tg ≈ 37 °C) induces two secondary relaxations (γ- and δ-) and primary relaxations (α-) for both enantiomeric compositions. After chemical purification of our samples by means of cooling recrystallization, no γ-process could be detected by DRS. Hence, it was highlighted that the molecular mobility in the glassy state is influenced by the presence of theophylline (TPH), the main impurity in DPL samples. We also proved that the dynamic behavior of a single enantiomer and the racemic mixture of the same purified compound are quasi-identical. This study demonstrates that the relative stability and the molecular mobility of chiral amorphous drugs are strongly sensitive to chemical purity.

Crystallization from the Amorphous State of a Pharmaceutical Compound: Impact of Chirality and Chemical Purity

The crystallization behavior and morphological features of particles obtained from amorphous diprophylline (DPL) are reported. After fast cooling of the melt, progressive heating above the glass transition (Tg ≈ 37 °C) induces the nucleation and growth of well-shaped crystals: PC for primary crystals. The combination of differential scanning calorimetry, hot stage optical microscopy, powder X-ray diffraction, and Raman spectroscopy revealed that these PC are kinetically favored and can form spontaneously in the supercooled melt whatever the enantiomeric composition, although their development and relative stability are influenced by the presence of theophylline, the main impurity in DPL samples. Specific crystal surfaces of the PC act as favorable areas and support for the subsequent formation of previously known metastable crystal forms consisting of solid solutions of the two DPL enantiomers. This study demonstrates the complex multistep mechanism that can occur during the temperature-induced crystalliz...

Monitoring isoniazid level in human fluids in the presence of theophylline using gold@platinum core@shell nanoparticles modified glassy carbon electrode

We report the electrochemical determination of anti-tuberculosis drug, isoniazid (INH) using gold–platinum core–shell nanoparticles (Au@PtNPs) modified glassy carbon electrode (GCE). The Au@PtNPs modified GCE was fabricated by electroless deposition of AuNPs by reducing HAuCl4 in the presence of NH2OH followed by the electroless deposition of PtNPs in the presence of H2PtCl6 and NH2OH. The initially deposited AuNPs act as the nucleation centre and catalyzed the deposition of PtNPs. Scanning electron microscopy (SEM) studies suggest that the electroless deposition of Pt on Au was isotropic and uniform. Then, the GC/Au@PtNPs electrode was exploited for the determination of INH in the presence of theophylline (TP). It was found that GC/Au@PtNPs electrode not only enhanced the oxidation currents of INH and TP but also shifted their potentials toward less positive potential in contrast to bare GCE. The present modified electrode was successfully used to determine these drugs simultaneously in a mixture. Selective determination of INH in the presence of 100-fold higher concentration of TP was also achieved at GC/Au@PtNPs electrode. The amperometric current response was increased linearly while increasing the concentration of INH from 50×10−9 to 100×10−6M with a correlation coefficient of 0.998 and the limit of detection was found to be 26×10−9M (S/N=3). Finally, the practical application of the present modified electrode was demonstrated by simultaneously determining the concentrations of INH and TP in human blood serum and urine samples.

Biomolecules Electrochemical Sensing Properties of a PMo11V@N-Doped Few Layer Graphene Nanocomposite

A novel hybrid nanocomposite, PMo11V@N-doped few layer graphene, was prepared by a one-step protocol through direct immobilization of the tetrabutylammonium salt of a vanadium-substituted phosphomolybdate (PMo11V) onto N-doped few layer graphene (N-FLG). The nanocomposite characterization by FTIR and XPS confirmed its successful synthesis. Glassy carbon modified electrodes with PMo11V and PMo11V@N-FLG showed cyclic voltammograms consistent with surface-confined redox processes attributed to Mo-centred reductions (MoVI→MoV) and a vanadium reduction (VV→VIV). Furthermore, PMo11V@N-FLG modified electrodes showed good stability and well-resolved redox peaks with high current intensities. The observed enhancement of PMo11V electrochemical properties is a consequence of a strong electronic communication between the POM and the N-doped few layer graphene. Additionally, the electro-catalytic and sensing properties towards acetaminophen (AC) and theophylline (TP) were evaluated by voltammetric techniques using a glassy carbon electrode modified with PMo11V@N-FLG. Under the conditions used, the square wave voltammetric peak current increased linearly with AC concentration in the presence of TP, but showing two linear ranges: 1.2 × 10−6 to 1.2 × 10−4 and 1.2 × 10−4 to 4.8 × 10−4 mol dm−3, with different AC sensitivity values, 0.022 A/mol dm−3 and 0.035 A/mol dm−3, respectively (detection limit, DL = 7.5 × 10−7 mol dm−3).