Aminophylline

Pharmaceutical safety testing requires a cheap, fast and highly efficient platform for real-time evaluation of drug toxicity and secondary effects. In this study, we have developed a microfluidic system for phenotype-based evaluation of toxic and teratogenic effects of drugs using zebrafish (Danio rerio) embryos and larvae as the model organism. The microfluidic chip is composed of two independent functional units, enabling the assessment of zebrafish embryos and larvae. Each unit consists of a fluidic concentration gradient generator and a row of seven culture chambers to accommodate zebrafish. To test the accuracy of this new chip platform, we examined the toxicity and teratogenicity of an anti-asthmatic agent-aminophylline (Apl) on 210 embryos and 210 larvae (10 individuals per chamber). The effect of Apl on zebrafish embryonic development was quantitatively assessed by recording a series of physiological indicators such as heart rate, survival rate, body length and hatch rate. Most importantly, a new index called clonic convulsion rate, combined with mortality was used to evaluate the toxicities of Apl on zebrafish larvae. We found that Apl can induce deformity and cardiovascular toxicity in both zebrafish embryos and larvae. This microdevice is a multiplexed testing apparatus that allows for the examination of indexes beyond toxicity and teratogenicity at the sub-organ and cellular levels and provides a potentially cost-effective and rapid pharmaceutical safety assessment tool.

BackgroundPediatric asthma has gained increasing concerns with poorly understood pathogenesis. The purpose of this study was to explore the associations of interleukin-4 (IL-4), IL-6, and IL-12 levels in peripheral blood (PB) with lung function, cellular immune function, and children's quality of life (QOL) with moderate-to-severe asthma.MethodsA total of 1158 children with moderate-to-severe asthma (the experimental group) and 1075 healthy children (the control group) were recruited for our study. Enzyme-linked immunosorbent assay was used to detect IL-4, IL-6, and IL-12 levels. T lymphocytes were detected by alkaline phosphatase antialkaline phosphatase, and erythrocyte immune was measured by red blood cell C 3b receptor (RBC-C3bR) rosette-forming test. The forced expiratory volume in 1 second (FEV1) and peak expiratory flow (PEF) were detected, after which FEV1/forced vital capacity (FVC) was calculated before and after treatment. PedsQL3.0 was used to measure the effect of asthma on QOL of children, and the correlation between IL-4, IL-6, and IL-12 levels and the lung function and QOL was measured. Logistic regression analysis was applied to detect related factors of moderate-to-severe asthma of children.ResultsAfter treatment, the decreased IL-4 and IL-6 levels and increased IL-12 level were revealed in the experimental group. The cellular immune function's disorder was significantly decreased, and an elevated CD3, CD4, CD8, and declined CD4/CD8 level was performed in T lymphocytes. RBC-C3bR was increased, and red blood cell immune complex (RBC-IC) was reduced in erythrocyte immune in comparison with those before treatment. Lung function parameters all increased. After treatment, the symptoms of asthma in children reduced with scores of increased QOL. IL-4 was positively related to RBC-IC, but negatively associated with the QOL score. IL-6 showed negative connection with CD4/CD8, RBC-C3bR, FEV1/FVC, and QOL score, and had positive connection with PEF. In addition, IL-12 was negatively correlated with PEF. The levels of IL-4, RBC-C3bR, FEV1/FVC, and PEF were independent risk factors for the prognosis of treatment for children with moderate-to-severe asthma.ConclusionThis study demonstrated that IL-4, IL-6, and IL-12 levels in PB were associated with lung function, cellular immune function, and QOL in children with moderate-to-severe asthma.

Pharmacologic reversal of serious or intolerable side effects (SISEs) from vasodilator stress is an important safety and comfort measure for patients experiencing such effects. While typically performed using intravenous aminophylline, recurrent shortages of this agent have led to a greater need to limit its use and consider alternative agents. This information statement provides background and recommendations addressing indications for vasodilator reversal, timing of a reversal agent, incidence of observed SISE with vasodilator stress, clinical and logistical considerations for aminophylline-based reversal, and alternative non-aminophylline based reversal protocols.

BackgroundProgesterone is known to maintain uterine quiescence as pregnancy advances. Recently, its efficacy in preventing preterm birth has been questioned prompting a search for an alternative treatment option. Cyclic AMP has been shown invitro to act in synergy with progesterone to maintain uterine quiescence.MethodsWe undertook an open label randomised feasibility study to test the hypothesis that the addition of aminophylline to the standard of care (SoC) is acceptable and can be tolerated in pregnant women at high risk of spontaneous preterm labour (sPTL). Women at high risk of sPTL, who met the inclusion criteria were invited to participate and randomised to receive the SoC (progesterone alone, n = 33) or treatment with the SoC and aminophylline (n = 37). The main outcome measure was to assess the how many women at high-risk of sPTL tolerated and continued to take aminophylline. Data were analysed using Graphpad Prism 8.0c (Graphpad Software, San Diego, CA, USA).ResultsWe found that of the addition of aminophylline was well tolerated in 30 of the 33 (91%) of women who continued in the combined arm, without any additional adverse maternal or fetal outcomes. 58% of eligible women agreed to participate in the study. The compliance rate was high at 99.42% +-0.82%. 67% of the women completed the post study questionnaire and all stated their willingness to take aminophylline if it were offered routinely for the prevention of sPTL.ConclusionsThe addition of aminophylline to the SoC is acceptable to women at high-risk of sPTL confirming that a randomised trial of aminophylline to reduce preterm delivery in women at high-risk of PTL is feasible.Trial registrationClinical trial gov NCT03152942. Date of full registration: 15/5/2017. https://clinicaltrials.gov/ct2/show/NCT03152942?cond=NCT03152942%26;draw=2%26;rank=1 .