UNASSIGNED: Theophylline was an orally administered xanthine used for treatment of apnea of prematurity and Bronchopulmonary Dysplasia in ambulatory follow-up of Low-Birth-Weight infants (LBWI) with oxygen-dependency in the outpatient Kangaroo Mother Care Program (KMCP). Theophylline\'s main metabolic product is caffeine; therefore, it was an alternative due to the frequent lack of ambulatory oral caffeine in low and middle-income countries.
UNASSIGNED: To assess the effectiveness of oral theophylline in decreasing days with oxygen and to describe frequency of adverse related events.
UNASSIGNED: Quasi-experiment before and after withdrawal of theophylline given systematically to LBWI with ambulatory oxygen in two KMCPs.
UNASSIGNED: 729 patients were recruited; period 1: 319 infants when theophylline was given routinely and period 2: 410 infants when theophylline was no longer used. The theophylline cohort had less gestational age, less weight at birth, more days in Neonatal Intensive Care Unit, more days of oxygen-dependency at KMCP admission, and more frequencies of Intrauterine Growth Restriction and apneas. After adjusting with propensity score matching, multiple linear regression showed that nutrition was associated with days of oxygen-dependency, but theophylline treatment not. No differences were found in frequencies of readmissions up to 40 weeks, intraventricular hemorrhage or neurodevelopmental problems. Participants in period 2 had more tachycardia episodes.
UNASSIGNED: We did not find association between oral theophylline treatment and the reduction of days with ambulatory oxygen. For the current management of oxygen-dependency in LBW infants, the importance of nutrition based on exclusive breast feeding whenever possible, is the challenge.

A 10-year-old spayed female shih tzu dog was brought to the hospital because of recurring syncope that occurred simultaneously with a cough. Physical examination did not reveal an abnormal heart rhythm or abnormal heart sounds. Electrocardiography revealed sinus arrest of 4.7 s with intermittent escape beats during coughing. Additional examinations, including thoracic radiography, clinical pathology, and echocardiography, revealed no abnormalities of concern. Forty-eight-hour Holter monitoring captured 1 syncopal episode following severe coughing, during which the longest sinus arrest lasted 16 s with intermittent escape beats. This observation confirmed our strong suspicion that coughing was the cause of varying degrees of sinus arrest in this dog. Theophylline, codeine, and short-term prednisolone were prescribed to treat the dog\'s cough. The daily episodes of syncope ceased and coughing decreased. Subsequent 48-hour Holter monitoring revealed no abnormal pauses, and the owner did not report syncope. Theophylline and codeine were continued for 5 mo, during which time no syncope occurred. To our knowledge, this case provides the first clear evidence of a correlation between cough-induced sinus arrest and syncope in a veterinary patient, as confirmed by Holter monitoring and electrocardiography. Key clinical message: Cough-induced severe bradycardia and syncope were identified in a shih tzu dog. After the antitussive medication was adjusted, the signs resolved.
Bradycardie sévère et syncope provoquées par la toux chez un chienUne chienne shih tzu stérilisée âgée de 10 ans a été amenée à l’hôpital en raison d’une syncope récurrente survenue simultanément avec une toux. L’examen physique n’a révélé aucun rythme cardiaque anormal ni bruits cardiaques anormaux. L’électrocardiographie a révélé un arrêt sinusal de 4,7 s avec des battements d’échappements intermittents lors de la toux. Des examens complémentaires, notamment une radiographie thoracique, des analyses en pathologie clinique et une échocardiographie, n’ont révélé aucune anomalie préoccupante. Une surveillance Holter de 48 heures a capturé 1 épisode syncopal à la suite d’une toux sévère, au cours duquel l’arrêt sinusal le plus long a duré 16 s avec des battements d’échappements intermittents. Cette observation a confirmé nos fortes suspicions selon lesquelles la toux était la cause de divers degrés d’arrêt sinusal chez ce chien. De la théophylline, de la codéine et de la prednisolone de courte durée ont été prescrites pour traiter la toux du chien. Les épisodes quotidiens de syncope ont cessé et la toux a diminué. Une surveillance Holter ultérieure de 48 heures n’a révélé aucune pause anormale et le propriétaire n’a pas signalé de syncope. La théophylline et la codéine ont été poursuivies pendant 5 mois, période pendant laquelle aucune syncope ne s’est produite. À notre connaissance, ce cas constitue la première preuve claire d’une corrélation entre l’arrêt sinusal induit par la toux et la syncope chez un patient vétérinaire, comme le confirme la surveillance Holter et l’électrocardiographie.Message clinique clé :Une bradycardie et une syncope sévères induites par la toux ont été identifiées chez un chien shih tzu. Après ajustement du traitement antitussif, les signes ont disparu.(Traduit par Dr Serge Messier).

A cost-effective, selective, sensitive, and operational TLC-densitometric approach has been adapted for the concurrent assay of Hydroxyzine Hydrochloride (HYX), Ephedrine Hydrochloride (EPH), and Theophylline (THP) in their pure powder and pharmaceutical forms. In the innovative TLC-densitometric approach, HYX, EPH, and THP were efficaciously separated and quantified on a 60F254 silica gel stationary phase with chloroform-ammonium acetate buffer (9.5:0.5, v/v) adjusted to pH 6.5 using ammonia solution as a mobile liquid system and UV detection at 220 nm. The novel TLC method validation has been performed in line with the international conference for harmonization (ICH) standards and has been effectively used for the estimation of the researched medicines in their pharmaceutical formulations without intervention from excipients. Additionally, parameters affecting the chromatographic analysis have been investigated. The new TLC approach\'s functionality and greenness were appraised using three modern and automated tools, namely the Blue Applicability Grade Index (BAGI), the Analytical Greenness metric (AGREE), and the Green Analytical Procedure Index (GAPI) tools. In short, the greenness characteristics were not achieved as a result of using mandatory, non-ecofriendly solvents such as ammonia and chloroform. On the contrary, the applicability and usefulness of the novel TLC approach were attained via concurrent estimation for the three drugs using simple and straightforward procedures. Moreover, the novel TLC method outperforms previously published HPLC ones in terms of the short run time per sample and moderate pH value for the liquid system. According to the conclusions of comparisons with previously recorded TLC methods, our novel HPTLC method has the highest AGREE score, so it is the greenest HPTLC strategy. Moreover, its functionality and applicability are very appropriate because of the simultaneous assessment of three drugs in one TLC run. Furthermore, no tedious and complicated extraction and evaporation processes are prerequisites.

The global prevalence of type 2 diabetes (T2D) is 10.5% among adults in the age range of 20-79 years. The primary marker of T2D is persistent fasting hyperglycemia, resulting from insulin resistance and β-cell dysfunction. Multiple factors can promote the development of T2D, including obesity, inflammation, and oxidative stress. In contrast, dietary choices have been shown to prevent the onset of T2D. Oatmeal, lean proteins, fruits, and non-starchy vegetables have all been reported to decrease the likelihood of T2D onset. One of the most widely consumed beverages in the world, coffee, has also demonstrated an impressive ability to reduce T2D risk. Coffee contains a diverse array of bioactive molecules. The antidiabetic effects of coffee-derived polyphenols have been thoroughly described and recently reviewed; however, several non-polyphenolic molecules are less prominent but still elicit potent physiological actions. This review summarizes the effects of select coffee-derived non-polyphenols on various aspects of T2D pathogenesis.

Recently, we compared an interplay of the adenosine system and nitric oxide (NO) in the regulation of renal function between male normoglycaemic (NG) and streptozotocin-induced diabetic rats (DM). Considering the between-sex functional differences, e.g., in the NO status, we present similar studies performed in female rats. We examined if the theophylline effects (non-selective adenosine antagonist) in NG and DM females with or without active NO synthases differed from the earlier findings. In anaesthetised female Sprague Dawley rats, both NG and DM, untreated or after NO synthesis blockade with L-NAME, theophylline effects, on blood pressure, renal hemodynamics and excretion, and renal tissue NO were investigated. Renal artery blood flow (Transonic probe), cortical, outer-, and inner-medullary flows (laser-Doppler technique), and renal tissue NO signal (selective electrode) were measured. In contrast to males, in female NG and DM rats, theophylline induced renal vasodilation. In NO-deficient females, theophylline induced comparable renal vasodilatation, confirming the vasoconstrictor influence of the renal adenosine. In NG and DM females with intact NO synthesis, adenosine inhibition diminished kidney tissue NO, contrasting with an increase reported in males. Lowered baseline renal excretion in DM females suggested stimulation of renal tubular reabsorption due to the prevalence of antinatriuretic over natriuretic tubular action of adenosine receptors. An opposite inter-receptor balance pattern emerged previously from male studies. The study exposed between-sex functional differences in the interrelation of adenosine and NO in rats with normoglycaemia and streptozotocin diabetes. The findings also suggest that in diabetes mellitus, the abundance of individual receptor types can distinctly differ between females and males.

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.

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.

UNASSIGNED: Theophylline has been used for decades in human medicine for its psychostimulant, anti-inflammatory, and bronchodilator effects. Historically, in pulmonary medicine, theophylline has been used in the treatment of obstructive pulmonary diseases such as bronchial asthma (BA) or chronic obstructive pulmonary disease (COPD). This review aims to determine whether theophylline still has its place in the therapy of obstructive pulmonary diseases or whether we can even extend its use to other diagnoses such as atropine-resistant cardiac arrests, apnea of prematurity, or others. Moreover, we also aim to determine if there is a rationale for using low-dose theophylline due to its immunomodulatory and anti-inflammatory effect, or if the future of methylxanthines lies in newly synthesized derivates of theophylline such as bamifylline, or doxofylline.
UNASSIGNED: The narrative review is based on a literature search of the articles indexed in the PubMed database in 2023. We searched the database since the year 2009 using the MeSH terms \"theophylline\", \"aminophylline\", and \"methylxanthines\" and we included original articles in the English language.
UNASSIGNED: Theophylline has a number of adverse drug reactions (ADRs), the most serious of which is its effect on the cardiovascular system. It can cause severe arrhythmias or even cardiac arrest when overdosed. On the other hand, there is still a substantial amount of its applications in current clinical practice.
UNASSIGNED: There is considerable controversy associated with its use in current medicine, which can be attributed both to its narrow therapeutic range and its mentioned cardiotoxic effect. Herein, we summarize the current state-of-art of theophylline and its use in human medicine.

OBJECTIVE: 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.
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.

Attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopic imaging is a powerful tool to visualize the distribution of components, and it has been used to analyze drug release from tablets. In this work, ATR-FTIR spectroscopic imaging was applied for observing the dissolution of molecular crystals from tablet compacts. The IR spectra provided chemically specific information about the transformation of crystal structures during the dissolution experiments. Theophylline (TPL) anhydrate and its cocrystals were used as model systems of molecular crystals. The IR spectra during the dissolution of TPL revealed information about the crystal structure of TPL, which transformed from anhydrate to monohydrate in water. During a dissolution test of a model cocrystal system, it was suggested that an active pharmaceutical ingredient (API) and a coformer were dissolved in water simultaneously. The IR spectra that were acquired during the dissolution of a cocrystal tablet showed new spectral bands attributed to the API after 5 min. This suggested that the precipitation of API was observed during the dissolution experiment. Measurements from ATR-FTIR spectroscopic imaging can visualize the drug release from the tablet and determine the transformation of molecular crystals during their dissolution. These results will have an impact on clarifying the dissolution mechanism of molecular crystals.