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Importance and objective: Self-reported caffeine consumption has been widely used in research while it may be subject to bias. We sought to investigate the associations between self-reported caffeine consumption and plasma levels of caffeine and its two main metabolites (paraxanthine and theophylline) in the community. Methods: Data from two population-based studies (SKIPOGH1 and 2 (N = 1246) and CoLaus|PsyCoLaus (N = 4461)) conducted in Switzerland were used. Self-reported caffeine consumption was assessed using questionnaires. Plasma levels of caffeine and its metabolites were quantified by ultra-high performance liquid chromatography coupled to a tandem quadrupole mass spectrometer. Results: In both studies, mean log plasma levels of caffeine and its two metabolites were over 6.48 (plasma levels = 652 ng/ml) when no caffeine consumption was reported. Subsequently, nonlinear associations between log plasma levels and self-reported caffeine consumption were observed in SKIPOGH, with a change of the slope at 3–5 cups of espresso per day in SKIPOGH1 but not SKIPOGH2. In CoLaus|PsyCoLaus, increased daily consumption of caffeinated beverages was associated with increased log plasma levels with a change of the slope at 3 cups. In both studies, declared caffeine consumption higher than 3–5 cups per day was not associated with higher plasma levels of caffeine and its metabolites. Conclusion: Self-reports of no or low caffeine consumption and consumption of more than 3–5 cups of coffee should be interpreted with caution, with possible under- or over-estimation. Quantifying plasma levels of caffeine and its metabolites may contribute to a better estimation of caffeine intake. [ABSTRACT FROM AUTHOR]

Objective: To explore the clinical value of Vitamin-D combined with budesonide/formoterol (BF) and theophylline sodium glycinate (TSG) sustained-release tablets in the treatment of patients with chronic obstructive pulmonary disease (COPD). Methods: Medical records of 114 patients with CODP, treated in Wenzhou Geriatric Hospital from October 2020 to February 2023, were retrospectively analyzed. Of them, 59 received treatment with Vitamin-D combined with BF and TSG sustained-release tablets (Group-A), and 55 patients received treatment with BF combined with TSG sustainedrelease tablets (Group-B). Lung function indicators, blood gas status, inflammatory factors, fractional exhaled nitric oxide (FeNO), and 25-hydroxyvitamin D [25(OH)D] levels before and after the treatment in both groups were collected. Results: After the treatment, lung function indicators, blood gas status, inflammatory factors, FeNO, and 25 (OH) D levels in both groups were significantly improved compared to pretreatment levels, and were significantly better in the Group-A compared to Group-B (P<0.05). Conclusions: The combination of Vitamin-D, BF, and TSG sustained-release tablets can effectively regulate the blood gas status of patients with COPD, improve lung function, regulate FeNO and 25 (OH) D, and effectively downregulate the levels of inflammatory factors, thus reducing the degree of inflammatory response. [ABSTRACT FROM AUTHOR]

AbstractIn this study, the structural, vibrational, and biological properties of Indacaterol and Theophylline were thoroughly investigated using quantum chemical and spectroscopic methods, and then compared with experimental FTIR, Raman, and UV–Vis data. The analysis revealed that electronegative oxygen and nitrogen atoms in both molecules facilitate charge transfers, resulting in the shortening of C–C bonds. The HOMO–LUMO energy gaps were found to be 4.298 eV for Indacaterol and 5.170 eV for Theophylline, indicating that Indacaterol is more bioactive. The electrophilic index values suggest that Indacaterol is more electrophilic, potentially offering a higher affinity for protein binding. Molecular electrostatic potential surface maps indicated that electrophilic regions are concentrated near the oxygen and nitrogen atoms, which was corroborated by molecular docking analysis. Binding affinities of Indacaterol and Theophylline to COVID-19 main protease proteins were calculated, showing higher affinities for Indacaterol. Drug likeness, physicochemical, and ADMET results suggest that both molecules have favorable pharmacokinetic profiles and comply with Lipinski’s Rule of Five, indicating effective absorption and distribution. Overall, the study suggests that Indacaterol and Theophylline could function as inhibitors against SARS-CoV-2 and COVID-19 proteins, with Indacaterol potentially being more effective. [ABSTRACT FROM AUTHOR]

Four new halogen-bonded cocrystals of biological methylxanthines, named caffeine, theophylline and theobromine, have been prepared with 1,4-diiodotetrafluorobenzene as a halogen bond donor by mechanochemical and solution processes. For theophylline, N⋯I and N⋯O interactions were observed, while for caffeine and theobromine, only N⋯I was detected. The solids were characterized by PXRD, SC-XRD, FTIR and thermal methods (TGA-DSC analyses). In addition, the solid-state photoluminescence properties of the methylxanthines and their respective cocrystals have been studied and quantum chemistry calculations have been performed to rationalise and understand the electronic and optical properties of all compounds. This work provides a triad of natural methylxanthines capable of forming halogen-bonded multicomponent systems that can give rise to a cocrystal-to-crystal transformation with off–on luminescence activation. [ABSTRACT FROM AUTHOR]

Ensuring the quality control of active pharmaceutical ingredients is crucial for drug products being introduced into the market. Even for established drugs, it is necessary to maintain a cutting-edge impurity control system. To analyze caffeine and chlorphenoxamine hydrochloride in their binary mixture, as well as theophylline and chlorphenoxamine N-oxide as related substances, a reversed phase-high performance liquid chromatography combined with a diode array detector system was created. The chromatographic separation was conducted using a C18 X-select Waters® column. The mobile phase consisted of 20.0 mM potassium dihydrogen phosphate modified to pH 3 with o-phosphoric acid and methanol. A gradient elution program was adopted at a flow rate of 1.3 mL/min and detected at a wavelength of 222 nm. The present methodology demonstrates a concentration ranging from 2–60, 1–80, 0.5–20 to 0.4–20 µg/mL for chlorphenoxamine hydrochloride, caffeine, chlorphenoxamine N-Oxide and theophylline, respectively. Chlorphenoxamine N-Oxide, being an impurity of chlorphenoxamine was prepared by refluxing intact drug with 5% H2O2 for 24 h at 100 °C. One of the objectives of the analytical community is to promote the adoption of green analysis methods, which involve the development of environmentally friendly techniques. The levels of greenness and whiteness were evaluated using four specific tools: Eco-Scale System, GAPI, AGREE, and RGB tool. Furthermore, we have evaluated the greenness of the analytical method presented and compared its performance and greenness to that of the approach described in the literature. In this study, results from CPX and CAF analysis were compared to those obtained in a previous study. The result shows that there is no notable variation in precision and accuracy. The proposed method was validated in accordance with the requirements of ICH. [ABSTRACT FROM AUTHOR]

Simple Summary: Caffeine is a natural substance found in coffee (Coffea spp.), cocoa (Theobroma cacao), cola (Cola nitida), guaraná (Paullinia cupana), maté (Ilex paraguariensis), and tea plant (Camellia sinensis). These plant species are widely used to produce different drinks and foods, generating a large volume of by-products that may be used for animal feed. This article is part of a broad study that aims to evaluate the safety of using by-products containing caffeine to feed laying hens. In this study, we show that the eggs of laying hens fed caffeine contain this compound together with its primary metabolites: theophylline, theobromine, and paraxanthine. It is essential to highlight that the levels of these compounds found in eggs do not appear to pose any health risk to consumers. This study aimed to determine whether the eggs of laying hens fed caffeine contain this compound and its primary metabolites (theophylline, theobromine, and paraxanthine). Laying hens were distributed into four experimental groups fed rations containing 0 (control), 150, 300, or 450 μg/g of caffeine. For residual analysis, six eggs per group were collected after 4, 8, and 12 weeks. The concentrations of caffeine, theophylline, theobromine, and paraxanthine were determined in the white and yolk of each egg by a high-performance liquid chromatography with photodiode array detector (HPLC-PDA) method. All four compounds were detected in the white and yolk of eggs produced by hens fed caffeine, but their levels in the egg white were approximately twice those in the yolk. The major metabolite found in eggs was theophylline (57.5% of caffeine metabolites in the egg white and 58.5% in the yolk), followed by theobromine (39.9% in the egg white and 41.5% in the yolk), and paraxanthine (2.64% in the egg white and non-detected in the yolk). In summary, caffeine and its metabolites, theophylline, theobromine, and paraxanthine, are transferred to the chicken eggs. [ABSTRACT FROM AUTHOR]

The present pilot study is as a part of Ph.D. Programme under THE TAMILNADU Dr. M.G.R Medical University. The study was designed to assess the effectiveness of Novel Designed Nebulizer (NDN) Compliance among Pre- schoolers undergoing nebulization in selected Hospital, Salem. Quasi experimental research design was adopt- ed. 20 children (10 experimental, 10 control group) who were admitted in pediatric wards with respiratory con- ditions and receiving nebulization between the age group of 3 to 6 years were selected by purposive sampling. Nebulization was given to experimental group with Novel Designed Nebulizer (NDN) and control group with routine nebulization. The results showed that the post test scores reveal that experimental group all 10(10%) the preschoolers were having high level of compliance and in control group all 10(10%) the preschoolers were having Medium level of compliance to nebulization procedure.The Friedman test value is 9.235 which is greater than the table value which indicates that the Novel designed nebulization is effective in increasing the compli- ance in experimental group.overall mean and SD in Experimental group is 2.31±0.23and the overall mean and SD in control group is 4.19 ±0.46. The mean difference is 1.88. The Z value is 3.800 which is higher than the table value which shows that the Novel designed nebulization is effective in improving the compliance among Preschoolers in experimental group. [ABSTRACT FROM AUTHOR]

Aim of the work: The study was conducted to evaluate the influence of theophylline pre-treatment on serum pharmacokinetics and milk elimination of tylosin following single intramuscular (IM) administrations in lactating goats. Methods and results: In a cross-over study, tylosin was injected via intramuscular (IM) at a single dose of 15 mg/kg b.wt. After a one-month washout period goats received theophylline at a daily IM dose of 2 mg/kg b.wt. for seven consecutive days then tylosin was injected IM dose of 15 mg/kg b.wt. two hours after the last theophylline dosing. Blood samples were collected before and at 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, and 24 h post-injection. Samples were left to clot and then centrifuged to yield serum. Milk samples were collected before and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 48, and 72 h post-injection from each goat by hand milking. Tylosin serum concentrations were determined by high-performance liquid chromatography (HPLC). Tylosin concentrations versus time were analyzed by a noncompartmental method. Tylosin Cmax significantly declined from 1.73 ± 0.10 to 1.01 ± 0.11 µg/ml, and attained Tmax values of 2 and 1 h, respectively in theophylline-pretreated goats. Moreover, theophylline pretreatment significantly shortened the elimination half-life (t1/2el) from 6.94 to 1.98 h, t1/2ka from 0.62 to 0.36 h and the mean residence time (MRT) from 8.02 to 4.31 h, also Vz/F and AUCs decreased from 11.91 to 7.70 L/kg and from 12.64 to 4.57 µg*h/ml, respectively, consequently, theophylline enhanced the clearance (Cl/F) of tylosin from the body. Similarly, tylosin milk concentrations were significantly lower in theophylline-pretreated goats than in goats that received tylosin alone and were detected up to 24 and 72 h in both groups, respectively. Moreover, the t1/2el and AUCs were significantly decreased from 14.68 ± 1.97 to 4.72 ± 0.48 h, and from 181 to 67.20 µg*h/ml, respectively. Conclusions: The withdrawal period for tylosin in goat milk is at least 72 h. Theophylline pretreatment significantly decreases serum and milk tylosin concentrations to subtherapeutic levels, which could have serious clinical consequences such as failure of therapy. This means that after administering tylosin to goats, milk from these animals should not be consumed for at least 96 h to ensure that the milk is free from residues of the antibiotic. [ABSTRACT FROM AUTHOR]

The receptor ability of diethyl N,N′‐(1,3‐phenylene)dicarbamate (1) to form host–guest complexes with theophylline (TEO) and caffeine (CAF) by mechanochemistry was evaluated. The formation of the 1–TEO complex (C12H16N2O4·C7H8N4O2) was preferred and involves the conformational change of one of the ethyl carbamate groups of 1 from the endo conformation to the exo conformation to allow the formation of intermolecular interactions. The formation of an N—H...O=C hydrogen bond between 1 and TEO triggers the conformational change of 1. CAF molecules are unable to form an N—H...O=C hydrogen bond with 1, making the conformational change and, therefore, the formation of the complex impossible. Conformational change and selective binding were monitored by IR spectroscopy, solid‐state 13C nuclear magnetic resonance and single‐crystal X‐ray diffraction. The 1–TEO complex was characterized by IR spectroscopy, solid‐state 13C nuclear magnetic resonance, powder X‐ray diffraction and single‐crystal X‐ray diffraction. [ABSTRACT FROM AUTHOR]

In pharmaceuticals, pseudo-polymorphism, e.g., the existence of hydrate and anhydrous forms, affects their physicochemical characteristics. Therefore, the evaluation of pseudo-polymorphism is one of the most important quality analyses. In this research, we investigate the real-time monitoring of the hydration reaction of theophylline using terahertz attenuated total reflection time domain spectroscopy (THz-attenuated total reflection (ATR)-TDS). We continuously measured a mixture of hydroxypropyl cellulose solution and theophylline anhydrous (TPA) while keeping it pressed to the ATR surface. We observed that the absorption peaks derived from TPA decreased and those derived from theophylline monohydrate (TPM) increased with time, demonstrating that the hydrate reaction of TPA can be monitored. Subsequently, we performed an accurate and quantitative evaluation of the hydration reaction by calculating the temporal changes in the crystal form ratio of TPM based on the changes in its second derivative peak intensity followed by a curve fitting. In addition, we performed real-time monitoring of the reaction using two different pressure mechanisms, finding that using a weight to apply pressure provided better reproducibility than using a screw. This study demonstrates that THz spectroscopy is a useful method for the evaluation of pseudo-polymorphism in pharmaceuticals. [ABSTRACT FROM AUTHOR]

Abstract Ensuring the quality control of active pharmaceutical ingredients is crucial for drug products being introduced into the market. Even for established drugs, it is necessary to maintain a cutting-edge impurity control system. To analyze caffeine and chlorphenoxamine hydrochloride in their binary mixture, as well as theophylline and chlorphenoxamine N-oxide as related substances, a reversed phase-high performance liquid chromatography combined with a diode array detector system was created. The chromatographic separation was conducted using a C18 X-select Waters® column. The mobile phase consisted of 20.0 mM potassium dihydrogen phosphate modified to pH 3 with o-phosphoric acid and methanol. A gradient elution program was adopted at a flow rate of 1.3 mL/min and detected at a wavelength of 222 nm. The present methodology demonstrates a concentration ranging from 2–60, 1–80, 0.5–20 to 0.4–20 µg/mL for chlorphenoxamine hydrochloride, caffeine, chlorphenoxamine N-Oxide and theophylline, respectively. Chlorphenoxamine N-Oxide, being an impurity of chlorphenoxamine was prepared by refluxing intact drug with 5% H2O2 for 24 h at 100 °C. One of the objectives of the analytical community is to promote the adoption of green analysis methods, which involve the development of environmentally friendly techniques. The levels of greenness and whiteness were evaluated using four specific tools: Eco-Scale System, GAPI, AGREE, and RGB tool. Furthermore, we have evaluated the greenness of the analytical method presented and compared its performance and greenness to that of the approach described in the literature. In this study, results from CPX and CAF analysis were compared to those obtained in a previous study. The result shows that there is no notable variation in precision and accuracy. The proposed method was validated in accordance with the requirements of ICH.

Abstract Aim of the work The study was conducted to evaluate the influence of theophylline pre-treatment on serum pharmacokinetics and milk elimination of tylosin following single intramuscular (IM) administrations in lactating goats. Methods and results In a cross-over study, tylosin was injected via intramuscular (IM) at a single dose of 15 mg/kg b.wt. After a one-month washout period goats received theophylline at a daily IM dose of 2 mg/kg b.wt. for seven consecutive days then tylosin was injected IM dose of 15 mg/kg b.wt. two hours after the last theophylline dosing. Blood samples were collected before and at 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, and 24 h post-injection. Samples were left to clot and then centrifuged to yield serum. Milk samples were collected before and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 48, and 72 h post-injection from each goat by hand milking. Tylosin serum concentrations were determined by high-performance liquid chromatography (HPLC). Tylosin concentrations versus time were analyzed by a noncompartmental method. Tylosin Cmax significantly declined from 1.73 ± 0.10 to 1.01 ± 0.11 µg/ml, and attained Tmax values of 2 and 1 h, respectively in theophylline-pretreated goats. Moreover, theophylline pretreatment significantly shortened the elimination half-life (t1/2el) from 6.94 to 1.98 h, t1/2ka from 0.62 to 0.36 h and the mean residence time (MRT) from 8.02 to 4.31 h, also Vz/F and AUCs decreased from 11.91 to 7.70 L/kg and from 12.64 to 4.57 µg*h/ml, respectively, consequently, theophylline enhanced the clearance (Cl/F) of tylosin from the body. Similarly, tylosin milk concentrations were significantly lower in theophylline-pretreated goats than in goats that received tylosin alone and were detected up to 24 and 72 h in both groups, respectively. Moreover, the t1/2el and AUCs were significantly decreased from 14.68 ± 1.97 to 4.72 ± 0.48 h, and from 181 to 67.20 µg*h/ml, respectively. Conclusions The withdrawal period for tylosin in goat milk is at least 72 h. Theophylline pretreatment significantly decreases serum and milk tylosin concentrations to subtherapeutic levels, which could have serious clinical consequences such as failure of therapy. This means that after administering tylosin to goats, milk from these animals should not be consumed for at least 96 h to ensure that the milk is free from residues of the antibiotic.

Objective(s): In the present study, the relaxant effect of crocetin on tracheal smooth muscle cells (TSM) and its possible mechanisms were evaluated. Materials and Methods: The study was conducted on 54 male Wistar rats in 8 groups. TSM was contracted by methacholine (10 μM) and KCl (60 mM), and the relaxant effects of four cumulative concentrations of crocetin, petal extract of saffron, and theophylline were examined on non-incubated and TSM incubated with propranolol, chlorpheniramine, diltiazem, atropine, glibenclamide, and indomethacin were investigated. Results: In non-incubated TSM contracted by methacholine or KCl, crocetin and theophylline showed concentration-dependent relaxant effects (all, P<0.001). However, various concentrations of crocetin showed significantly lower relaxant effects compared to those of theophylline (all, P<0.001). In the methacholine-induced contraction of TSM, the relaxation effect of the last concentration of crocetin in the TSM incubated with propranolol was lower than in non-incubated TSM (P<0.05). In the incubated TSM with chlorpheniramine, the relaxant effects of the two last concentrations of crocetin were significantly lower than in the non-incubated tissues contracted by KCl (P<0.05 and P<0.0). The levels of EC50 crocetin in the incubated TSM with glibenclamide, chlorpheniramine, and indomethacin were markedly lower than in non-incubated (all, P<0.05). Conclusion: The results showed potent relaxation effects of crocetin on TSM and were suggested to be through stimulation of ß-adrenergic receptors, inhibition of histamine (H1 ) receptors, and potassium channel opening mechanisms. [ABSTRACT FROM AUTHOR]

A candidate reference measurement procedure (RMP) for serum theophylline via isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed. With a single-step precipitation pretreatment and a 6-min gradient elution, the method achieved baseline separation of theophylline and its analogs on a C18-packed column. A bracketing calibration method was used to ensure repeatable signal intensity and high measurement precision. The intra-assay and inter-assay imprecisions were 1.06%, 0.84%, 0.72% and 0.47%, 0.41%, 0.25% at concentrations of 4.22 µg/mL (23.40 µmol/L), 8.45 µg/mL (46.90 µmol/L), and 15.21 µg/mL (84.43 µmol/L), respectively. Recoveries ranged from 99.35 to 102.34%. The limit of detection (LoD) was 2 ng/mL, and the lowest limit of quantification (LLoQ) was 5 ng/mL. The linearity range extended from 0.47 to 60 µg/mL (2.61–333.04 µmol/L). No ion suppression and carry-over (< 0.68%) were observed. The relative bias for this candidate RMP that participated in 2023 External Quality Control for Reference Laboratories (RELA) conducted by the International Federation of Clinical Chemistry (IFCC) was within a range of 0.17 to 0.93%. Furthermore, two clinical immunoassay systems were compared with this candidate RMP, demonstrating good correlations. The results of the Trueness Verification Plan indicate significant differences among routine systems, highlighting the need for standardization efforts. The developed candidate RMP for serum theophylline serves as a precise reference baseline for standardizing clinical systems and assigning values to reference materials. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effect of oral theophylline on stent-related syndrome (SRS) after Double-J insertion. Background: Double-J stent is widely using in many urological procedures. Infection, hematuria, and discomfort are some of common complication after stenting. Theophylline is a dimethylated xanthine that inhibits phosphodiesterase and blocks adenosine receptors. To relaxing effect of theophylline on smooth muscles and its effects on the urinary system, it seems it could reduce complications after inserting Double-J stent especially ureteral stent syndrome. Method: In this double-blind placebo-controlled randomized clinical trial, 67 patients were enrolled. Mean (SD) age of control and theophylline group was 51.8 (12.5) and 43.9 (10.4) years old, respectively. Patients were randomized into two groups of control and theophylline. All patients were stenting with silicon Double J. Theophylline group received 100 mg of theophylline, twice daily for 30 days, while control group received placebo. Stent symptoms were assessed by questionnaire and urine culture was performed before stent removal at removal day. Statistical analysis was performed using Chi-squared test and t test with P < 0.05 considered significant. Logistic regression models were fitted, crudely and adjusted for age and sex. Result: Of 67 eligible patients, 60 completed the study. Theophylline significantly decreased percentages of gross hematuria (P < 0.001), dysuria (P < 0.001), and urinary frequency (P < 0.001). Microscopic hematuria (P = 0.042) and chills (P = 0.042) also decreased after theophylline. Conclusion: Theophylline could be an effective and safe choice for reducing SRS among patients undergoing Double-J stent insertion. [ABSTRACT FROM AUTHOR]

This study used micro-analyses, (FTIR, UV-Vis) spectra, magnetic, thermogravimetric, X-ray powder diffraction (XRD) patterns, and transmittance electron microscopy (TEM) techniques to characterize three synthesized theophylline (TPH) complexes with ruthenium(III), platinum(IV), and iridium(III) metal ions. The metal ions indicated above were found to align with the TPH drug chelate as a mono-dentate ligand via the deprotonated NH group at the nitrogen atom position N7, as verified by FTIR measurements. Additionally, the complexes conductivity and magnetic susceptibility were examined. The octahedral geometry for the synthesized complexes was proposed by the current data. Except for the iridium(III) complex, which has a non-electrolytic nature due to the presence of a chlorine atom inside the chelation sphere, the molar conductivity of the complexes in DMSO solution was electrolyte in nature. Theophylline complexes with a (metal: ligand) stoichiometry of 1:2 were produced. The TPH complexes have also been tested in vitro against G(+) bacteria (Bacillus subtilis and Staphylococcus Aureus) and G(-) bacteria (Pseudomonas aeruginosa and Escherichia coli) to evaluate their antibacterial efficacy. Human breast and liver cancer cell lines were used as a test for the TPH complexes in vitro anti-cancer properties. [ABSTRACT FROM AUTHOR]

Texturing metallic zinc anodes (MZAs) for selective exposure of (002)Zn plane with high thermodynamical stability is an efficient scheme for dendrite‐free Zn electrodeposition. However, fundamental factors that influence Zn deposition morphology via surface crystallographic texture engineering are not well understood. Herein, different from traditional cognition, MZAs with preferential exposure of (101)Zn facet are demonstrated to be equally effective in promoting dendrite‐free Zn deposition, which is enabled by introducing trace amount (0.01 m) of theophylline into ZnSO4 electrolyte. Experimental results and mathematical model corroborate, indicating mechanistically that the theophylline derived cations preferentially adsorb on the (002)Zn crystal plane due to higher adsorption energy, thereby accelerating its growth through increased binding affinity with Zn2+ ions. Consequently, this phenomenon facilitates the texture exposure of (101)Zn facet to achieve ordered surface crystallographic orientation of MZAs (101‐Zn), thus enabling electrodeposition/dissolution cycling over 650 h under a depth of discharge up to 40% and significantly boosting the rechargeability (76.7% capacity retention after 1000 cycles) of the 101‐Zn||carbon‐cloth@MnO2 full battery relative to counterpart without theophylline additive (36.3%). The work offers deep insights on the scientific links between the surface crystallographic orientation of MZAs and Zn deposition morphology, while opens up vast untapped opportunities to realize dendrite‐free MZAs. [ABSTRACT FROM AUTHOR]

Theophylline, a nitrogen-containing heterocycle, serves as a promising focal point for medicinal researchers aiming to create derivatives with diverse pharmacological applications. In this work, we present an improved synthetic method for a range of theophylline-1,2,4-triazole-S-linked N-phenyl acetamides (4a-g) utilizing ultrasound-assisted synthetic approach. The objective was to assess the effectiveness of synthesized theophylline-1,2,4-triazoles (4a-g) as inhibitors of HCV serine protease and as antibacterial agents against B. subtilis QB-928 and E. coli AB-274. Theophylline-1,2,4-triazoles were obtained in good to excellent yields (69%-95%) in a shorter time than conventional approach. 4-Chlorophenyl moiety containing theophylline-1,2,4-triazole 4c displayed significantly higher inhibitory activity against HCV serine protease enzyme (IC50 = 0.015 ± 0.25 mg) in comparison to ribavirin (IC50 = 0.165 ± 0.053 mg), but showed excellent binding affinity (-7.55 kcal/mol) with the active site of serine protease, better than compound 4c (-6.90 kcal/mol) as well as indole-based control compound 5 (-7.42 kcal/mol). In terms of percentage inhibition of serine protease, 2-chlorophenyl compound 4b showed the maximum percentage inhibition (86%), more than that of the 3,4-dichlorophenyl compound 4c (76%) and ribavirin (81%). 3,4-Dimethylphenyl-based theophylline-1,2,4-triazole 4g showed the lowest minimum inhibitory concentration (MIC = 0.28 ± 0.50 μg/ mL) against the B. subtilis bacterial strain as compared to the standard drug penicillin (MIC = 1 ± 1.50 μg/mL). The other 4-methylphenyl theophylline-1,2,4-triazole 4e (MIC = 0.20 ± 0.08 μg/mL) displayed the most potent antibacterial potential against E. coli in comparison to the standard drug penicillin (MIC = 2.4 ± 1.00 μg/mL). Molecular docking studies further helped in an extensive understanding of all of the interactions between compounds and the enzyme active site, and DFT studies were also employed to gain insights into the molecular structure of the synthesized compounds. The results indicated that theophylline-linked triazole derivatives 4b and 4c showed promise as leading contenders in the fight against the HCV virus. Moreover, compounds 4e and 4g demonstrated potential as effective chemotherapeutic agents against E. coli and B. subtilis, respectively. To substantiate these findings, additional in vivo studies and clinical trials are imperative, laying the groundwork for their integration into future drug design and development. [ABSTRACT FROM AUTHOR]

The facile fabrication is reported of highly electrochemically active Ti3C2Tx MXene/MWCNT (3D/1D)-modified screen-printed carbon electrode (SPE) for the efficient simultaneous electrochemical detection of paracetamol, theophylline, and caffeine in human blood samples. 3D/1D Ti3C2Tx MXene/MWCNT nanocomposite was synthesized using microwave irradiation and ultrasonication processes. Then, the Ti3C2Tx/MWCNT-modified SPE electrode was fabricated and thoroughly characterized towards its physicochemical and electrochemical properties using XPS, TEM, FESEM, XRD, electrochemical impedance spectroscopy, cyclic voltammetry, and differential pulse voltammetry techniques. As-constructed Ti3C2Tx-MWCNT/SPE offers excellent electrochemical sensing performance with good detection limits (0.23, 0.57, and 0.43 µM) and wide linear ranges (1.0 ~ 90.1, 2.0 ~ 62.0, and 2.0–90.9 µM) for paracetamol, caffeine, and theophylline, respectively, in the human samples. Notably, the non-enzymatic electroactive nanocomposite-modified electrode has depicted a semicircle Nyquist plot with low charge transfer resistance (Rct∼95 Ω), leading to high ionic diffusion and facilitating an excellent electron transfer path. All the above results in efficient stability, reproducibility, repeatability, and sensitivity compared with other reported works, and thus, it claims its practical utilization in realistic clinical applications. [ABSTRACT FROM AUTHOR]

The term non-cardiac syncope includes all forms of syncope, in which primary intrinsic cardiac mechanism and non-syncopal transient loss of consciousness can be ruled out. Reflex syncope and orthostatic hypotension are the most frequent aetiologies of non-cardiac syncope. As no specific therapy is effective for all types of non-cardiac syncope, identifying the underlying haemodynamic mechanism is the essential prerequisite for an effective personalized therapy and prevention of syncope recurrences. Indeed, choice of appropriate therapy and its efficacy are largely determined by the syncope mechanism rather than its aetiology and clinical presentation. The two main haemodynamic phenomena leading to non-cardiac syncope include either profound hypotension or extrinsic asystole/pronounced bradycardia, corresponding to two different haemodynamic syncope phenotypes, the hypotensive and bradycardic phenotypes. The choice of therapy—aimed at counteracting hypotension or bradycardia—depends on the given phenotype. Discontinuation of blood pressure–lowering drugs, elastic garments, and blood pressure–elevating agents such as fludrocortisone and midodrine are the most effective therapies in patients with hypotensive phenotype. Cardiac pacing, cardioneuroablation, and drugs preventing bradycardia such as theophylline are the most effective therapies in patients with bradycardic phenotype of extrinsic cause. [ABSTRACT FROM AUTHOR]

Hydroxypropyl methylcellulose (HPMC) is a preferred hydrophilic matrix former for controlled release formulations produced through continuous twin-screw wet granulation. However, a non-homogeneous API distribution over sieve fractions with underdosing in the fines fraction (<150 µm) was previously reported. This could result in content uniformity issues during downstream processing. Therefore, the current study investigated the root cause of the non-homogeneous theophylline distribution. The effect of process parameters (L/S-ratio and screw configuration) and formulation parameters (matrix former and filler type) on content uniformity was studied. Next, the influence of the formulation parameters on tableting and dissolution behavior was investigated. Altering the L/S-ratio or using a more aggressive screw configuration did not result in a homogeneous API distribution over the granule sieve fractions. Using microcrystalline cellulose (MCC) as filler improved the API distribution due to its similar behavior as HPMC. As excluding HPMC or including a hydrophobic matrix former (Kollidon SR) yielded granules with a homogeneous API distribution, HPMC was identified as the root cause of the non-homogeneous API distribution. This was linked to its fast hydration and swelling (irrespective of the HPMC grade) upon addition of the granulation liquid. [ABSTRACT FROM AUTHOR]

Background: Drug release from controlled release delivery systems is influenced by various factors, including the polymer's grade and the drug's hydration form. This study aimed to investigate the impact of these factors on the controlled release of theophylline (THN). This research compares the monohydrate form found in branded products with the anhydrous form in generic equivalents, each formulated with different polymer grades. Methods: Quality control assessment was conducted alongside in vitro evaluation, complemented by various analytical techniques such as X-ray diffraction (XRD) and scanning electron microscopy (SEM). Additionally, thermal analyses using differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) were employed. Results: Quality control assessments demonstrated that the generic tablets exhibited lower average weight and resistance force compared to the branded ones. In vitro tests revealed that generic tablets released contents within 120 min, compared to 720 min for the branded counterpart. Characterization using XRD and SEM identified disparities in crystallinity and particle distribution between the three samples. Additionally, the thermal analysis indicated consistent endothermic peaks across all samples, albeit with minor variations in heat flow and decomposition temperatures between the two products. Conclusions: This study demonstrated that variations in polymer grade and hydration form significantly impact THN release. [ABSTRACT FROM AUTHOR]

In this work, we explored the convenient and sustainable method for the synthesis of 1, 8 dioxodecahydroacridine derivatives was achieved via a one-pot condensation reaction of dimedone, para-nitrobenzaldehyde, and ammonium acetate by using theophylline as a catalyst at room temperature in aqueous medium. This environmentally friendly method boasts several notable features, including high product yields, rapid completion of reactions, the use of eco-friendly and bio-based catalysts, straightforward work-up procedures without the need for column chromatography, cost-effectiveness, clean synthesis practices that avoid the use of harmful organic solvents, and exceptional atom efficiency. [ABSTRACT FROM AUTHOR]

Background: Theophylline (THN), a bronchodilator with potential applications in emerging conditions like COVID-19, requires a controlled-release delivery system due to its narrow therapeutic range and short half-life. This need is particularly crucial as some existing formulations demonstrate impaired functionality. This study aims to develop a new 12-h controlled-release matrix system (CRMS) in the form of a capsule to optimize dosing intervals. Methods: CRMSs were developed using varying proportions of poloxamer 407 (P-407), stearyl alcohol (STA), and hydroxypropyl methylcellulose (HPMC) through the fusion technique. Their in vitro dissolution profiles were then compared with an FDA-approved THN drug across different pH media. The candidate formulation underwent characterization using X-ray diffraction, scanning electron microscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, and thermogravimetric analysis. Additionally, a comprehensive stability study was conducted. Results: In vitro studies showed that adjusting the concentrations of excipients effectively controlled drug release. Notably, the CRMS formulation 15 (CRMS-F15), which was composed of 30% P-407, 30% STA, and 10% HPMC, closely matched the 12 h controlled-release profile of an FDA-approved drug across various pH media. Characterization techniques verified the successful dispersion of the drug within the matrix. Furthermore, CRMS-F15 maintained a consistent controlled drug release and demonstrated stability under a range of storage conditions. Conclusions: The newly developed CRMS-F15 achieved a 12 h controlled release, comparable to its FDA-approved counterpart. [ABSTRACT FROM AUTHOR]

Copyright of Hungarian Medical Journal / Orvosi Hetilap is the property of Akademiai Kiado and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Cacao seeds, Theobroma cacao, provide the basis for a ceremonially important Mesoamerican food. Past efforts to identify cacao in ceramics focused on highly decorative vessel forms associated with elite ceremonial contexts, creating assumptions as to how cacao was distributed and who could access it. This study examines 54 archaeological ceramic sherds from El Pilar (Belize/Guatemala) of Late Classic (600 to 900 CE) residential and civic contexts representing a cross-section of ancient Maya inhabitants. Identification of cacao in ancient sherds has depended on the general presence of theobromine; we used the discrete presence of theophylline, a unique key biomarker for cacao in the region. Analysis was done by grinding off all outside surfaces to reduce contamination, pulverizing the inner clay matrix, extracting absorbed molecules, and concentrating the extractions. In order to obtain especially high selectivity and low limits of detection, our study utilized the technique of resonance-enhanced multiphoton ionization coupled with laser-desorption jet-cooling mass spectrometry. This technique isolates molecules in the cold gas phase where they can be selectively ionized through a resonant two-photon process. Of the sherds analyzed, 30 samples (56%) were found to contain significant amounts of theophylline and thus test positive for cacao. Importantly, cacao is present in all contexts, common to all Maya residents near and far from centers.

Purpose: To revise the IVIVC considering the physiologically sound Finite Absorption Time (F.A.T.) and Finite Dissolution Time (F.D.T.) concepts. Methods: The estimates τ and τd for F.A.T. and F.D.T., respectively are constrained by the inequality τd ≤ τ; their relative magnitude is dependent on drug's BCS classification. A modified Levy plot, which includes the time estimates for τ and τd was developed. IVIVC were also considered in the light of τ and τd estimates. The modified Levy plot of theophylline, a class I drug, coupled with the rapid (30 min) and very rapid (15 min) dissolution time limits showed that drug dissolution/absorption of Class I drugs takes place in less than an hour. We reanalyzed a carbamazepine (Tegretol) bioequivalence study using PBFTPK models to reveal its complex absorption kinetics with two or three stages. Results: The modified Levy plot unveiled the short time span (~ 2 h) of the in vitro dissolution data in comparison with the duration of in vivo dissolution/absorption processes (~ 17 h). Similar results were observed with the modified IVIVC plots. Analysis of another set of carbamazepine data, using PBFTPK models, confirmed a three stages absorption process. Analysis of steady-state (Tegretol) data from a paediatric study using PBFTPK models, revealed a single input stage of duration 3.3 h. The corresponding modified Levy and IVIVC plots were found to be nonlinear. Conclusions: The consideration of Levy plots and IVIVC in the light of the F.A.T. and F.D.T. concepts allows a better physiological insight of the in vitro and in vivo drug dissolution/absorption processes. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

1-Methylxanthine is a high-value derivative of caffeine of limited natural availability with many potential pharmaceutical applications. Unfortunately, production of 1-methylxanthine through purely chemical methods of synthesis are unfavorable due to lengthy chemical processes and the requirement of hazardous chemicals, ultimately resulting in low yields. Here, we describe a novel biosynthetic process for the production of 1-methylxanthine from theophylline using engineered Escherichia coli whole-cell biocatalysts and reaction optimization. When scaled-up to 1590 mL, the simple biocatalytic reaction produced approximately 1188 mg 1-methylxanthine from 1444 mg theophylline, constituting gram-scale production of 1-methylxanthine in as little as 3 hours. Following HPLC purification and solvent evaporation, 1163 mg of dried 1-methylxanthine powder was collected, resulting in a 97.9 wt% product recovery at a purity of 97.8%. This is the first report of a biocatalytic process designed specifically for the production and purification of the high-value biochemical 1-methylxanthine from theophylline. This process is also the most robust methylxanthine N -demethylation process featuring engineered E. coli to date, capable of gram-scale production. • Novel, biosynthetic pathway for production of 1-methylxanthine at gram scale. • Engineered E. coli for high-value biochemical production. • High performance liquid chromatography (HPLC) separation for high purity. • Co-factor (NADH) recycle through by-product (formaldehyde) degradation. [ABSTRACT FROM AUTHOR]

Currently, nasal administration of active pharmaceutical ingredients is most commonly performed using swirl-nozzle-based pump devices or pressurized syringes. However, they lead to limited deposition in the more active regions of the nasal cavity, especially the olfactory region, which is crucial for nose-to-brain drug delivery. This research proposes to improve deposition in the olfactory region by replacing the swirl nozzle with a nanoengineered nozzle chip containing micrometer-sized holes, which generates smaller droplets of 10–50 μm travelling at a lower plume velocity. Two nanotech nozzle chips with different hole sizes were tested at different inhalation flow rates to examine the deposition patterns of theophylline, a hyposmia treatment formulation, using a nasal cavity model. A user study was also conducted and showed that the patient instructions influenced the inhalation flow rate characteristics. Targeted flow rates of between 0 and 25 L/min were used for the in vitro deposition study, yielding 21.5–31.5% olfactory coverage. In contrast, the traditional swirl nozzle provided only 10.8% coverage at a similar flow rate. This work highlights the potential of the nanotech soft mist nozzle for improved intranasal drug delivery, particularly to the olfactory region. [ABSTRACT FROM AUTHOR]

Caffeine (CF) is a metabolic probe drug used in the determination of the hepatic drug‐oxidizing capacity. The aim of this study was to investigate temporal changes in the hepatic drug‐oxidizing capacity using plasma metabolite/CF ratios in non‐pregnant goats (n = 11) and pregnant goats (n = 23). CF (5 mg/kg, intravenous) was administered in six periods (Period 1–6) with 45 days between two periods. The plasma levels of CF and its metabolites, theophylline (TP), theobromine (TB) and paraxanthine (PX), were determined by HPLC‐UV. To evaluate hepatic drug‐oxidizing capacity in terms of enzymes that play a role in CF metabolism, the plasma metabolic ratios including TB/CF, PX/CF, TP/CF and TB + PX + TP/CF were determined at 10 h following CF administration. Plasma metabolite/CF ratios were similar between non‐pregnant and pregnant goats. However, plasma metabolite/CF ratios in Period 3 (45 days in pregnant goats) were significantly higher than those other periods in both pregnant and non‐pregnant goats. The effect of pregnancy may not be observed on drugs that are substrates of enzymes involved in CF metabolism in goats. [ABSTRACT FROM AUTHOR]

Copyright of Erzincan University Journal of Science & Technology is the property of Erzincan Binali Yildirim Universitesi and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Food Safety & Quality is the property of Journal of Food Safety & Quality Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The use of syntonic engineering (SE), or synthonic modelling has been increasing in the pharmaceutical industry. This study used the Material Studio and HABIT98 programs to model the intermolecular (synthonic) interactions, lattice energetics, and morphology prediction. Two organic systems representing common active ingredients and excipients were selected, Theophylline (TH) and D-mannitol (DM). The Nemethy and Dreiding force fields (FF) paired with matching semiempirical chargers were used for all SE calculations for all case studies. For both systems, hydrogen bonding OH...H was the dominating interaction. The interatomic stability for TH was mainly contributed by the amino nitrogen making amide the primary functional group. In DM, interatomic stability was attributed to the hydrogen atom, making hydroxyl the primary functional group. TH was crystallised as needle-like, while DM was dendritic. [ABSTRACT FROM AUTHOR]