Serum Theophylline Research Articles

Evaluation and clinical application of a bracketing calibration-based isotope dilution liquid chromatography-tandem mass spectrometry candidate reference measurement procedure for serum theophylline.

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.

Dietary patterns suggest that dark chocolate intake may have an inhibitory effect on oral cancer: a Mendelian randomization study.

Previous studies reported that variations in dietary intake patterns substantially impact human health, specifically tumorigenesis. However, confounding factors in previous cohort studies have obscured the relationship between dietary differences and the risk of oral cancer (OC). We developed an outcome dataset from genome-wide association studies (GWAS) data on three OCs within the GAME-ON project, using GWAS-META merging. We extracted 21 dietary exposures, including 10 dietary patterns, 6 vitamins, and 5 micronutrients, from the UK Biobank database, using the inverse variance weighting method as the primary statistical method. Sensitivity analysis was conducted to detect heterogeneity and pleiotropy. Serum metabolite concentrations were adjusted using multivariate Mendelian randomization. Of the 10 analyzed dietary patterns, 8 showed no significant association with the risk of developing OC. Consumption of dark chocolate (inverse variance weighted [IVW]: Odds ratio (OR) = 0.786, 95% confidence interval [CI]: 0.622-0.993, p = 0.044) and sweet pepper exhibited an inverse relationship with OC risk (IVW: OR = 0.757, 95% CI: 0.574-0.997, p = 0.048). Reverse MR analysis revealed no reverse causality. Furthermore, no significant correlation was observed between the intake of 6 vitamins and 5 micronutrients and the risk of developing OC. After using multivariable MR to adjust for serum caffeine, linoleate, theophylline, and theobromine metabolism levels, consuming dark chocolate was unrelated to a decreased risk of OC. After adjusting each serum metabolite individually, the observed p-values deviated from the original values to varying degrees, indicating that the components of dark chocolate could have different effects. Among these components, theophylline demonstrated the most significant inhibitory effect. This study demonstrated a causal relationship between the intake of dark chocolate and sweet peppers and a lower risk of OC. The components of dark chocolate could have different effects.

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.

Increasing sensitivity and selectivity for electrochemical sensing of uric acid and theophylline in real blood serum through multinary nanocomposites

The sensing of theophylline (TP) and uric acid (UA) is important for the diagnosis and treatment of diseases in the early stages. While the first proofs show the potential of electrochemical sensors, the simultaneous detection of TP and UA is still not satisfactory. Herein we present an electrochemical sensor showing high sensitivity and selectivity for the detection of the two purine derivatives, TP and UA in blood serum. Key for this is a multinary nanocomposite which was specially designed for the sensing purpose and is based on titania nanoparticles, copper oxide, and boron-doped reduced graphene oxide, Au nanoparticles as also the modification of the supporting carbon electrode with 2-amino-5-mercapto-1,3,4-thiadiazole through electropolymerization. The study showed that the multinary nanocomposite improves the electrochemically active surface area and the electron transfer rate of the sensor, which together boosts the current response for the sensing strongly. It could be shown that the electrochemical sensor provides an excellent linear relationship between 0.5 nM and 10.0 µM for UA and for TP between 1.0 nM and 10.0 µM. Detection limits of 0.18 nM and 0.36 nM results for UA and TP, respectively. The sensitivity is 1.27 μA µM−1 cm−2 for UA and 1.06 μA µM−1 cm−2 for TP. Additionally, the method was used for the simultaneous measurements of UA and TP in real blood serum, which demonstrated the excellent applicability of the device.

The characteristics and costs of severe theophylline toxicity in a tertiary critical care unit in Eastern Cape Province, South Africa.

Severe theophylline toxicityrequiring haemodialysisaccounts for approximately one-third of drug toxicity cases admittedto theLivingstone Tertiary Hospital (LTH) intensive care unit (ICU) in Gqeberha, South Africa, imposing a significant resource burden. To investigate the characteristics and burden of severe theophylline toxicity in an Eastern Cape Province tertiaryhospital adult ICU. A retrospective review of all severe theophylline toxicity admissions to the ICU from 1 January 2013 to 31 December 2018 was conducted. Demographic and clinical data were captured and analysed. The National Department of Health 2019 fees schedule was used to calculate costs based on duration of ICU stay and number of haemodialysis sessions received. Of the 57 patients included in the study, 84% were cases of deliberate self-harm. The majority were aged <40 years (77%) and female (79%). The mean (standard deviation (SD)) initial serum theophylline level was 612 (269) µmol/L. Complications included convulsions (n=12; 21%), arrhythmias (n=9; 16%), need for mechanical ventilation (n=7; 12%) and death (n=4; 7%). The main risk factors for these complications were age ≥30 years, an inappropriately normal or elevated initial serum potassium level, an elevated serum creatinine kinase level and an elevated initial serum theophylline level. Receiver operator characteristic curve analysis assessing the initial serum theophylline level as a discriminator for life-threatening complications produced an area under the curve of 0.71 for serum theophylline >400 µmol/L (sensitivity 88%, specificity 12%). All the 4 patients who died had an initial serum theophylline level >1 000 µmol/L. The mean (SD) cost per admission amounted to ZAR16 897 (10 718), with a mean of one 4-hour dialysis session per admission. Severe theophylline toxicity, usually in the context of deliberate self-harm, is a preventable yet life-threatening toxicity encountered at LTH. Demographic risk factors include young females from certain areas in and around Gqeberha. Risk factors for complications include olderage, paradoxically normal or elevatedserumpotassiumlevels, elevatedserumcreatinine kinaselevelsandan initial serum theophylline level >400 µmol/L.Patients with these clinical features should be closely monitored and treated timeously at an appropriate level of care.The need for ICU admission and dialysis, both limited resources, makes the treatment of severe theophylline toxicity costly. Further studies of the underlying psychosocial drivers, local prescribing practicesand preventive interventionsrelated to severe theophylline toxicityare required.

Smell Changes and Efficacy of Nasal Theophylline (SCENT) irrigation: A randomized controlled trial for treatment of post-viral olfactory dysfunction

ObjectiveTo evaluate the efficacy and safety of intranasal theophylline saline irrigation on olfactory recovery in patients with post-viral olfactory dysfunction (PVOD). MethodsBetween May 2019 and April 2020, we conducted a double-blinded, placebo-controlled randomized clinical trial of adults with 6–36 months of PVOD. Patients were randomized to nasal theophylline saline irrigation or placebo saline irrigation twice a day for 6 weeks. The primary outcome was the Global Rating of Smell Change. Secondary outcomes were changes in the University of Pennsylvania Smell Identification Test (UPSIT) and Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS). ResultsTwenty-two patients (n = 12, theophylline; n = 10, placebo) completed the study. Slightly more patients in the theophylline group (33%) reported improved smell compared to the placebo group (30%, difference 3.3%, 95% CI -35.6% to 42.3%). The median differences in pre- and post-treatment UPSIT and QOD-NS change between the two groups were 1 (95% CI -3 to 5) and -10 (95% CI -15 to -4), respectively in favor of theophylline. Three patients receiving theophylline and 2 receiving placebo had clinically meaningful improvements on the UPSIT (difference 5%, 95% CI -30% to 40%). There were no adverse events, and serum theophylline levels were undetectable in 10/10 patients. ConclusionsWhile safe, there were no clinically meaningful differences in olfactory change between the two groups except for olfaction-related quality of life, which was better with theophylline. The imprecise estimates suggest future trials will need substantially larger sample sizes or treatment modifications, such as increasing the theophylline dose, to observe larger treatment effects.

Novel designed electrochemical sensor for simultaneous determination of linezolid and meropenem pneumonia drugs

• Layer by layer method is applied to fabricate GC/Gr/CNT-HQ/Fe-Ni sensor for electrochemical determination of LN and ME in human blood serum. • Practically determination of LN and ME in human serum is successfully accomplished in a wide concentration ranges with low detection limits of 0.97 nM and 1.3 nM respectively. • The sensor can efficiently be used for concurrent determination of three antibiotic drugs namely LN, ME, and TH in human serum. • Excellent interference resistance, good reproducibility and perfect storage stability are the features of the GC/Gr/CNT-HQ/Fe-Ni sensor. Treatment of pneumonia by only one antibiotic drug is difficult due to the involvement of several microorganisms in pneumonia disease as Methicillin-resistant Staphylococcus aureus (MRSA) and Klebsiella. Thus introducing another antibiotic drug meropenem (ME) beside the linezolid (LN) are usually used for treatment of pneumonia cases. Layer by layer method is applied to fabricate sensor for electrochemical determination of LN and ME in human blood serum. A glassy carbon surface (GC) is modified with a thin layer of graphene (Gr) followed by casting two consecutive thin layers of carbon nanotubes- hydroquinone mixture (CNT-HQ) and Fe-Ni alloy nanoparticles; GC/Gr/CNT-HQ/Fe-Ni. The current signals enhancement is due to the synergism of all the sensor components. Voltammetry determination of LN and ME in human serum is successfully accomplished in the concentration ranges (0.007–12 µM) and (0.01–12 µM) with low detection limits of 0.97 nM and 1.3 nM, respectively. Also, the sensor can efficiently be used for concurrent determination of three antibiotic drugs namely LN, ME and theophylline (TH) in human serum. The GC/Gr/CNT-HQ/Fe-Ni sensor is practically used in human serum samples for LN and ME determination with satisfactory recoveries, outstanding interference resistance and good stability.

Serum Theophylline Concentrations in very Preterm Neonates Receiving Intravenous Aminophylline for Apnea

Objective: To determine the percentage of neonates who achieved therapeutic theophylline level (TTL) after receiving standard IV loading/maintenance aminophylline doses. To assess factors associated with achieving therapeutic theophylline concentrations and to describe adverse effects of aminophylline. Materials and Methods: This was a pilot, cross-sectional study. Preterm neonates ≤34 weeks’ gestation for which aminophylline was indicated for treatment of apnea were enrolled. Standard IV aminophylline dosage is 8 mg/ kg loading dose, followed by 1.5 mg/kg maintenance dose every 8 hours. Serum theophylline concentrations were measured prior to the 8th maintenance dose. Descriptive statistics, univariate and multivariate analyses were performed. Results: Twenty-five neonates (52% female) were enrolled: mean (standard deviation) gestational age and birth weight were 30.4 (2) weeks and 1,277 (415) grams, respectively. Aminophylline was initiated at a median (25%tile, 75%tile) postnatal age of 4 (1, 8) days. Baseline heart rate prior to the loading dose was 153 (13) beats-per-minute. Sixty percent of neonates achieved a therapeutic theophylline level. In the univariate analysis, being male and postnatal age ≤5 days were associated with successfully achieving a TTL. After adjusting for gender, postnatal age ≤5 days was the only factor associated with achieving a TTL (adjusted odds ratio 17.7, 95% confidence interval: 1.9, 164.4). Tachycardia and feeding intolerance were observed in 44% and 24% of neonates, respectively. Conclusion: Current IV aminophylline dosing conditions in Thailand achieved TTL in approximately two-thirds of neonates, suggesting therapeutic drug monitoring is beneficial for guiding dosing. A higher maintenance dose could be considered for neonates older than 5 days.

AHA statement addresses growing list of drugs that induce arrhythmias

AHA statement addresses growing list of drugs that induce arrhythmias

Eco-friendly synthesis of aloe vera plant extract decorated iron tungstate nanorods immobilized Nafion for selective and sensitive determination of theophylline in blood serum, black tea and urine samples

Abstract This paper describes a selective and sensitive detection of bronchodilators drug (theophylline) using aloe vera plant extract decorated iron tungstate nanorods (AFW) immobilized Nafion (Nf) modified glassy carbon electrode (GCE) (AFW/Nf/GCE). The AFW was synthesized by the co-precipitation method and characterized by UV-visible spectroscopy, x-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), elemental analysis (EDX) and electrochemical studies. Interestingly, the oxidation of theophylline with AFW/Nf/GCE displayed, a superior electrocatalytic activity, when compared with bare GCE and iron tungstate (FW) modified GCE. Besides, oxidation of theophylline in electrochemical sensor revealed that the tremendous current response linear ranges from 0.1-160μM and low detection limit (LOD) 0.0028μM. The electrochemical sensor studies showed a tremendous selectivity in biological and food samples. Besides, it showed manifested stability and reproducibility. The proposed method has been applied for the selective determination of theophylline in real samples such as human serum, black tea, and urine samples.

Age-Associated Theophylline Metabolic Activity Corresponds to the Ratio of 1,3-Dimethyluric Acid to Theophylline in Mice.

Age is known as one of influencing factor for theophylline (TP)-metabolizing capacity. In a previous our study, the ratio of TP and its major metabolite 1,3-dimethyluric acid (DMU) in serum (DMU/TP) is a useful index to estimate TP-metabolizing capacity, and this value markedly increased by influencing factor, such as the history of smoking. However, it is unknown whether DMU/TP values in serum reflect age-associated changes of TP-metabolizing capacity. In this study, the effect of age on the DMU/TP values in serum were investigated using mice of different age due to the limited blood sampling in human. The concentrations of TP and its metabolites in mouse serum were simultaneously measured using HPLC. As observed in human serum, serum TP concentrations were closely correlated with DMU concentration in mice, which indicates that the DMU/TP ratio is a good indicator of TP metabolic ability in mice. When TP was administered subcutaneously in 2-28-week-old mice, age-associated changes in the DMU/TP ratio in mice were observed. In conclusion, age-associated changes in TP-metabolizing capacity can be estimated by the DMU/TP ratio in serum.

Troponine I versus Creatinine Kinase-MB as Predictor Markers of the Severity and Outcomes in Acute Theophylline Toxicity

Theophylline is a bronchodilator drug that is used in the treatment of asthma and chronic obstructive pulmonary diseases. Cardiovascular complications contribute to morbidity and mortality that associate acute theophylline intoxication. The current study aimed to investigate troponin I and creatine kinase-MB as predictors of the severity and outcomes in cases of acute theophylline intoxication. This prospective cohort study included thirty one patients with acute theophylline toxicity admitted to Tanta Poison Control Center during the period from the first of March 2018 to the end of February 2019. Patients were subjected to personal and toxicological history taking, vital signs collection, grading of acute theophylline toxicity and measurement of serum theophylline level. Both troponin I and creatine kinase-MB were measured at admission and 12 hours post admission. Results revealed that, troponin I at time of admission and 12 hours post admission in addition to creatine kinase-MB 12 hours post admission were significantly higher in cases with severe acute theophylline intoxication and patients who required intensive care unit admission. It was concluded that, troponin I could predict the severity and the requirement of intensive care unit admission in acute theophylline toxicity either with early or delayed presentation. On the other hand, creatine kinase-MB could be considered for patients with delayed presentation.

Carbon nanoparticle-protected RNA aptasensor for amplified fluorescent determination of theophylline in serum based on nuclease-aided signal amplification

A carbon nanoparticle (CNP) and Cryonase-aided method that realizes the amplified fluorescent detection of theophylline was proposed. The amplification technique exploits distinct binding affinities of CNP towards the FAM-labeled theophylline RNA aptamer (aptasensor) and aptasensor/theophylline complex as well as the protection effect of CNP for absorbed aptasensor from enzymatic digestion by Cryonase. Upon the addition of theophylline, it forms an aptasensor/theophylline complex with a fluorescent dye-tagged aptasensor that is initially absorbed and quenched by CNP. The nuclease activity of Cryonase towards detached aptasensor probes is then activated, leading to efficient cleavage of aptasensor probes and separation of the fluorescent dye from the CNP surface. Theophylline that has been liberated can launch another reaction cycle, which ensures the sensitivity enhancement. A detection limit is achieved as high as 6.3 nM, which is 400-fold better than traditional strategies. The proposed sensing system also provides desired selectivity even in serum samples. The assay is simple, sensitive, selective, and universal, and has great promise for the design and application of aptasensors in the biological, chemical, and biomedical fields.

A retrospective study of theophylline-based therapy with tracheal collapse in small-breed dogs: 47 cases (2013-2017).

Theophylline acts as a bronchodilator and has an anti-inflammatory effect. In addition, theophylline can be applied in patients where there are concerns regarding the side-effects of corticosteroids. This retrospective case series evaluated theophylline-based therapy in tracheal collapse (TC) canine patients. Forty-seven dogs with TC that received theophylline-based therapy during 2013–2017 were investigated. A fluoroscopic examination was performed to diagnose and grade TC. Theophylline was prescribed (7.5–30 mg/kg PO q12h) and the theophylline serum concentrations were measured. Coughing was assessed using a coughing scoring scale. The mean coughing score decreased after the theophylline-based therapy compared with that observed before treatment. Clinical improvements were observed in 46/47 patients (97.9%). As the intrathoracic TC grading increased, the final theophylline dosage also increased (p value 0.019). The symptom-free period (SFP) with therapy was 189.7 ± 194.45 days (range, 0–720 days) and there was no statistically significant correlation between the SFP and age, sex, or TC grade on fluoroscopy. Although theophylline has generally been used as a third-line treatment, it was used as the main treatment in this study and most patients showed improvements. Dogs have a wider therapeutic index of serum concentrations than humans, and any undesirable effects were easily overcome. With further research, this therapy may prove to be a useful approach, but its safety for long-term use in the treatment of canine TC patients needs to be established.

Real time detection of adenosine and theophylline in urine and blood samples using graphene modified electrode

Herein, we report the grafting of stable graphene layers on to glassy carbon (GC) electrode by a two-step diazotization strategy using melamine. The resulting graphene modified electrode is used for the selective determination of theophylline (TP) in the presence of inhibitor neurotransmitter antagonist, adenosine (AD). The modified electrode surfaces are characterized by scanning electron microscopy (SEM) and cyclic voltammetry (CV). Bare GC electrode fails to show stable voltammetric signals for TP and AD due to the surface fouling caused by the oxidation products of the analytes. However, the graphene modified electrode showed stable voltammetric signals for the simultaneous detection of TP and AD than the bare GC electrode. Further, the graphene modified electrode is used for the selective determination of TP in the presence of 34-fold excess AD. A linear plot is noticed upon increasing the TP concentration from 3.0 × 10−8-1.0 × 10−4 M. The limit of detection is found to be 5.4 × 10−9 M (S/N = 3). The practical application of the proposed modified electrode is demonstrated by the simultaneous determination of TP and AD in human blood serum and urine samples.

Biomarker repurposing: Therapeutic drug monitoring of serum theophylline offers a potential diagnostic biomarker of Parkinson's disease.

Caffeine has been considered a neuroprotective agent against Parkinson’s disease (PD). Recent metabolomic analysis showed that levels of caffeine and its metabolites were decreased in sera from patients with PD compared with those from healthy controls. We focused on theophylline, which is one of the primary caffeine metabolites, as a candidate biomarker of PD because: (1) its serum level can be measured in hospital laboratories by standardized immunoassay kits for therapeutic drug monitoring and (2) because it is less markedly affected by caffeine intake. This was a pilot study to measure the levels of theophylline in sera of 31 patients with PD and 33 age-matched disease controls using an immunoassay kit. We confirmed the previous finding of significantly lower levels of serum theophylline in the PD group compared with control group (PD: 0.07±0.09 μg/mL, control: 0.18±0.24 μg/mL, p<0.05). Using such an approach of applying known medical biomarkers for neurodegenerative diseases may allow us to skip the process from the discovery phase to clinical application, and subsequently shorten the period of time necessary for biomarker development.

Predictors for Intensive Care Unit Admission in Acute Theophylline Intoxicated Patients

Theophylline remains the most widely pharmaceuticals for the treatment of acute and chronic asthma in several developing countries, as it is effective, cheap, and widely available. Few studies were investigated to predict the need of ICU admission based on clinical parameters recorded at admission. Hence, this study aimed to identify the predictors for ICU admission in acute theophylline intoxicated patients. It was carried out on one hundred and ten acutely theophylline poisoned patients who were admitted to Poison Control Unit, Emergency Hospital, Tanta University over a period of two years. For each patient, full sociodemographic, toxicological, clinical examination and routine laboratory investigations & serum theophylline level were done. Then, all findings of acute theophylline poisoned patients were analyzed against ICU admission. Statistical significant associations were found between ICU admission and gender, dose, CNS manifestations (agitations, hallucinations and tremors), hypotension, serum potassium and serum theophylline level. Logistic regression of clinically relevant variable showed that, patients who presented with hallucination, agitation, or hypotension had an increased likelihood of requiring admission to ICU and could correctly predicted 98.2% of cases. ROC curve analysis of serum theophylline accuracy revealed that, serum level ≥ 37.5 mg/L is a fair predictor for ICU admission. It could be concluded that, in acute theophylline intoxicated patients, hallucination, agitation and hypotension could be considered as good predictors for ICU admission. While, patients who had serum theophylline level ≥ 37.5 mg/L should be admitted in ICU as high risk patients.

Serum theophylline after multiple dosing with transdermal gels in cats.

Our objectives were, first, to determine if therapeutic serum theophylline concentrations could be achieved using long-term, once-daily dosing of transdermal theophylline and, secondarily, to evaluate the difference between two transdermal theophylline formulations. Seven healthy cats, 1-10 years of age, were evaluated in a two-way, randomized, double-blinded, crossover study. Participants received transdermal theophylline at 15 mg/kg for 21 days in either pluronic lecithin organogel (PLO) or Lipoderm formulation. On day 22, blood was collected 2, 6, 14 and 24 h after dosing. After a 14 day washout period, blood was collected to verify non-detectible theophylline concentrations. The alternate formulation was administered for 21 days, and sampling was repeated. Serum theophylline concentrations were determined using an automated immunoassay. Serum concentrations were compared between formulations using a two-way random-measures ANOVA and over time within a formulation using a repeated-measures ANOVA. Therapeutic serum theophylline concentrations were achieved for 2/7 cats in each group. Of 56 serum theophylline measurements obtained, only seven (13%) were within the therapeutic range. No significant difference was detected in drug concentrations achieved by the transdermal formulations at any time point. In addition, no significant difference in serum theophylline concentrations was noted between time points for PLO ( P = 0.751) or Lipoderm ( P = 0.107). Once-daily transdermal dosing of theophylline does not reliably achieve therapeutic concentrations. Individual cats may achieve therapeutic concentrations. No significant difference was noted between PLO and Lipoderm formulations. Therefore, transdermal theophylline formulations should not be considered as a first-line therapy in feline asthma patients.

Factors affecting the efficacy and safety of aminophylline in treatment of apnea of prematurity in neonatal intensive care unit

The factors affecting the safety and efficacy of aminophylline use in the treatment of apnea of prematurity (AOP) in the neonatal intensive care unit (NICU) are not clear. In this study, we aimed to evaluate the potential factors affecting the efficacy and safety of aminophylline in AOP treatment at standard doses and to determine appropriate patients for this therapy. Over a 3-year period (January 2012 to December 2014), the medical records of 206 preterm infants with apnea who were admitted to the NICU of our hospital to receive aminophylline infusions were retrospectively reviewed. These infants were subjected to routine theophylline monitoring by reversed-phase high performance liquid chromatography. The primary outcome measures were the efficacy of aminophylline treatment and adverse reactions observed upon administration. One-hundred and twenty-seven (61.65%) infants were considered to have undergone effective therapy and classified accordingly. Gestational age, body weight at the initiation of aminophylline, and serum theophylline concentration were identified as protective factors of therapeutic efficacy. Receiver operating characteristic (ROC) analysis indicated cutoff values of 30.36 weeks for gestational age and 1.69kg for body weight at initiation of aminophylline administration for ensuring high efficacy of aminophylline for AOP. Fifty-three (25.73%) infants had adverse reactions. Birth weight and serum concentration of theophylline were associated with an increased risk of adverse reactions, with odds ratios of 0.167 and 1.346, respectively. The ROC curves indicated a birth weight cutoff value of 1.48kg. Infants with apnea and gestational age >30.36 weeks, body weight at initiation of aminophylline treatment above 1.69kg, and birth weight >1.48kg are suitable for treatment with aminophylline. Monitoring of serum theophylline concentration should be implemented in the absence of clinical response or in case of suspected adverse reactions.

Simultaneous determination of theophylline and caffeine on novel [Tetra-(5-chloroquinolin-8-yloxy) phthalocyanato] manganese(III)-Carbon nanotubes composite electrode

This work reports the synthesis of new symmetrically substituted manganese(III) phthalocyanine (2eOHMnPc) (2) containing tetra 5-chloroquinolin-8-yloxy group at the peripheral position for the first time. Manganese(III) phthalocyanine (2) was synthesized by cyclotetramerization of 4-(5-chloroquinolin-8-yloxy)phthalonitrile (1) in the presence of corresponding metal salt (manganese(II) chloride). This peripherally substituted phthalocyanine complex (2) was purified by column chromatography and characterized by several techniques such as IR, mass and UV–Visible spectral data. This novel synthesized phthalocyanine was mixed with multiwalled carbon nanotubes in order to prepare the novel catalytic surface on glassy carbon electrode for theophylline and caffeine detection in acidic medium. The novel composite electrode surfaces were characterized by scanning electron microscopy and electrochemical impedance spectroscopy. Individual and simultaneous determination of theophylline and caffeine were studied by differential pulse voltammetry. The detection limits were individually calculated for theophylline and caffeine as 6.6 × 10−9 M and 5.0 × 10−8 M, respectively. In simultaneous determination, LODs were calculated for theophylline and caffeine as 8.1 × 10−9 M and 3.0 × 10−7 M, respectively. The practical applicability of the proposed modified electrode was tested for the determination of theophylline and caffeine in green tea, cola and theophylline serum.