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

Severe theophylline toxicity requiring haemodialysis accounts for approximately one-third of drug toxicity cases admitted to the Livingstone Tertiary Hospital (LTH) intensive care unit (ICU) in Gqeberha, South Africa, imposing a significant resource burden.Objectives. To investigate the characteristics and burden of severe theophylline toxicity in an Eastern Cape Province tertiary hospital adult ICU.Methods. 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.Results. 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.Conclusion. 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 older age, paradoxically normal or elevated serum potassium levels, elevated serum creatinine kinase levels and an 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 practices and preventive interventions related to severe theophylline toxicity are required.

Guia Prático de Atualização no tratamento da exacerbação de asma na criança e no adolescente ­ Posicionamento conjunto da Associação Brasileira de Alergia e Imunologia e Sociedade Brasileira de Pediatria / Practical Update Guide on the treatment of asthma exacerbation in children and adolescents ­ Joint position of the Brazilian Association of Allergy and Immunology and the Brazilian Society of Pediatrics

Exacerbação aguda de asma é uma condição frequente na criança e no adolescente e uma das causas mais comuns de procura aos pronto atendimentos e de internações. Pode ocorrer em pacientes que ainda não foram diagnosticados como asmáticos, e mesmo naqueles cujo controle da doença não se encontre adequado. Reconhecer a exacerbação e iniciar seu tratamento desde o domicílio até o adequado manejo inicial em ambiente hospitalar é fundamental para evitar sua evolução para complicações que coloquem o paciente em risco de vida. O tratamento compreende o reconhecimento e tratamento da hipoxemia, da obstrução e do processo inflamatório, além de fornecer orientações na alta hospitalar e encaminhamentos para continuidade do tratamento.

Acute exacerbation of asthma is a frequent condition in children and adolescents and one of the most common causes of seeking emergency care and hospitalization. It can occur in patients who have not yet been diagnosed with asthma, and even in those whose disease control is not adequate. Recognizing the exacerbation and starting its treatment from home until proper initial management in a hospital environment is essential to avoid its evolution to complications that put the patient at risk of life. Treatment comprises the recognition and treatment of hypoxemia, obstruction, and the inflammatory process, in addition to providing guidance at hospital discharge and referrals for continued treatment.

Efficacy and safety of combined doxofylline and salbutamol in treatment of acute exacerbation of chronic obstructive pulmonary disease

SUMMARY OBJECTIVE: The aim of this study was to investigate the efficacy and safety of combined doxofylline and salbutamol in the treatment of acute exacerbation of chronic obstructive pulmonary disease. METHODS: A total of 68 acute exacerbation of chronic obstructive pulmonary disease patients were randomly divided into control group (34 cases) and experimental group (34 cases), who received the doxofylline treatment and combined doxofylline and salbutamol treatment for 1 week, respectively. During the treatment, the remission time of typical respiratory manifestations was recorded, and the adverse reactions were observed. At the end of treatment, the treatment efficacy was evaluated. Before and after treatment, the pulmonary function indexes and serological indicators were detected. RESULTS: After treatment, compared with control group, in experimental group, the effective rate of treatment was significantly increased (p<0.05), the remission time of typical respiratory manifestations was significantly shortened (p<0.05), the pulmonary function indexes were significantly improved (p<0.05), the serum high-sensitivity C-reactive protein and cystatin C levels were significantly decreased, respectively (p<0.05), and the serum prealbumin level was significantly increased (p<0.05). In addition, the adverse reaction rate had no significant difference between two groups (p>0.05). CONCLUSIONS: In the treatment of acute exacerbation of chronic obstructive pulmonary disease, the combined use of doxofylline and salbutamol can quickly relieve the respiratory symptoms, mitigate the pulmonary dysfunction, and reduce the inflammatory response, thus promoting the outcome of patients.

Opioid-free general anesthesia and induced recovery from anesthesia in a patient with myotonic dystrophy type-1: a case report / Anestesia geral sem opioide e recuperação induzida da anestesia em paciente com distrofia miotônica tipo-1: relato de caso

Abstract Myotonic dystrophy type-1 (Steinert disease) is an autosomal dominant, progressive multisystem disease in which myotonic crisis can be triggered by several factors including pain, emotional stress, hypothermia, shivering, and mechanical or electrical stimulation. In this report, dexmedetomidine-based general anesthesia, in combination with a thoracic epidural for laparoscopic cholecystectomy in a patient with Steinert disease, is presented. An Aintree intubation catheter with the guidance of a fiberoptic bronchoscope was used for intubation to avoid laryngoscopy. Prolonged anesthetic effects of propofol were reversed, and recovery from anesthesia was accelerated using an intravenous infusion of theophylline.

Resumo A Distrofia Miotônica (DM) tipo-1 (Doença de Steinert) é uma doença multissistêmica progressiva autossômica dominante em que a crise miotônica pode ser desencadeada por vários fatores, incluindo dor, estresse emocional, hipotermia, tremores e estímulo mecânico ou elétrico. O presente relato descreve anestesia geral realizada com dexmedetomidina em combinação com peridural torácica para colecistectomia laparoscópica em paciente com Doença de Steinert. Para evitar laringoscopia, a intubação traqueal foi realizada utilizando cateter de intubação Aintree guiado por broncofibroscopia óptica. Os efeitos anestésicos prolongados do propofol foram revertidos e a recuperação anestésica foi acelerada pelo uso de infusão intravenosa de teofilina.

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.

Effect and Mechanism of Phosphodiesterase Inhibitors on Trabecular Outflow

PURPOSE: Phosphodiesterase (PDE) inhibitors increase matrix metalloproteinase (MMP) production by inhibiting re-uptake of adenosine and may potentiate nitric oxide (NO) activity. This study was performed to investigate the effects and mechanisms of PDE inhibitors on trabecular outflow in cultured human trabecular meshwork cells (HTMCs). METHODS: Primary HTMC cultures were exposed to 0, 20, and 50 µM dipyridamole (DPD) or theophylline (TPN). Permeability through the HTMC monolayer was assessed using carboxyfluorescein. The production of NO was assessed using the Griess assay and MMP-2 levels were measured via Western blotting. RESULTS: DPD significantly increased permeability accompanied with increased nitrite concentration and MMP-2 levels (all p 0.05). When treated with DPD and TPN together, both permeability and nitrite production were increased; however, MMP-2 levels showed no difference compared to DPD exposure alone (p > 0.05). CONCLUSIONS: DPD increased trabecular permeability accompanied with increased nitrite production and MMP-2 levels. PDE inhibitors may increase trabecular outflow by increasing MMP-2 levels and by potentiating NO activity through cyclic GMP in HTMC.

Inhaled Corticosteroids in Asthma and the Risk of Pneumonia

PURPOSE: Asthma is a common disease that is expensive and burdensome for patients. Inhaled corticosteroids (ICS) are the most important drugs for asthma treatment and are often prescribed long-term. However, the use of ICS has been reported to increase pneumonia, though this remains controversial. We evaluated whether the use of ICS increases the risk of pneumonia in asthmatic patients using the Health Insurance Review and Assessment Service (HIRA) database in Korea. METHODS: The Asthma Management Adequacy Assessment was performed by the HIRA in Korea. Patients with claimed insurance benefits for asthma disease codes and who were prescribed asthma medications more than 2 times were enrolled. Patient demographics, asthma medications, healthcare use, and complications were analyzed. RESULTS: The total number of asthma patients was 831,613. Patients using ICS were older and had more comorbidities than those not using ICS; they also visited outpatient clinics and emergency departments, and were more often hospitalized. Pneumonia and other complications occurred more often in patients using ICS, and they used more respiratory medications, except for theophylline. Multiple logistic regression analysis showed that ICS prescription was associated with pneumonia (odds ratio, 1.38; 95% confidence interval, 1.36-1.41). Age, sex, medical care, use of secondary and tertiary hospitals, and hospitalization due to asthma in the previous year were also associated with pneumonia. CONCLUSIONS: ICS use was associated with increasing pneumonia in asthmatic patients in Korea. Therefore, it is critical to acknowledge that the use of ICS may increase the risk of pneumonia and should be meticulously monitored in asthmatics.

Construction and application of theophylline-activated RNA switches in the regulation of expression of recombinant proteins in Bacillus subtilis / 生物工程学报

Bacillus subtilis can be widely used as an important microorganism for metabolic engineering and recombinant proteins expression in industrial biotechnology and synthetic biology. However, it is difficult to make accurate regulation of exogenous gene by biological tools in B. subtilis, which limits the application of B. subtilis in synthetic biology. The purpose of this study is to develop regulatory tools for precise control of gene expression by using non-coding RNAs, by which the activation of heterologous gene could be achieved without the auxiliary protein factors. We constructed the synthetic riboswitch E and aptazyme AZ using the theophylline aptamer. Six different native promoters from B. subtilis were functionally adapted with the E and AZ to fabricate an array of novel regulatory elements activated by theophylline. Then, we determined the performance of these elements using green fluorescence protein as reporter, and then further verified using red fluorescence protein and pullulanase as cargo proteins. Results showed that the same kind of RNA elements with different promoters showed different levels of efficiency. Promoter PsigW and E combination (sigWE) had the highest induction rate in B. subtilis. Compared with the control group, it can produce the induction rate of 16.8. Promoter PrpoB and AZ combination (rpoBAZ) showed the highest induction rate of 6.2. SigWE mediated mCherry induction rate was 9.2, and P43E mediated pullulanase induction rate was 32.8, in which enzyme activity reached 81 U/mL. This study confirmed that GFP, mCherry and pullulan can all be regulated by riboswitch and aptazyme, but there were differences between different combinations of promoters with RNA regulators.

The Effect of Theophylline on Improvement of Renal Function in Asphyxiated Neonates: A Systematic Review and Meta-analysis

The purpose of this systematic review and meta-analysis was to assess the preventive effect of theophylline on acute kidney injury and the ameliorative effect of theophylline on renal function in asphyxiated neonates. A literature search of the PubMed/Medline, Embase, and Cochrane Library databases for information published up to February 2019 was conducted. All studies that reported the incidence rate of acute kidney injury, serum creatinine level, and glomerular filtration rate after the randomized administration of theophylline or placebo were included. In total, eight studies involving 498 neonates were eligible. The incidence rate of acute kidney injury was significantly lower in the theophylline group than in the placebo group (risk ratio [RR]: 0.42, 95% confidence interval [CI]: 0.32–0.55, p < 0.001). The changes in serum creatinine level in the theophylline group were significantly higher than those in the placebo group from the first day of life to 3 and 5 days of age (weighted mean difference [WMD]: −0.51, 95% CI: −0.62 to −0.40, p < 0.001, and WMD: −0.26, 95% CI: −0.34 to −0.18, p < 0.001, respectively). The changes in glomerular filtration rate in the theophylline group were significantly higher than those in the placebo group from the first day of life to 3 days of age and the last day of follow-up (WMD: 12.30, 95% CI: 9.39–15.21, p < 0.001, and WMD: 9.35, 95% CI: 6.43–12.27, p < 0.001, respectively). These results suggested that theophylline has a beneficial effect on the prevention of acute kidney injury in neonates with perinatal asphyxia.

The Detailed Kinetics of Cytomegalovirus-specific T cell Responses after Hematopoietic Stem Cell Transplantation: 1 Year Follow-up Data

The detailed kinetics of the cytomegalovirus (CMV)-specific T cell response in hematopoietic stem cell transplant (HCT) recipients have not yet been fully assessed. We evaluated these kinetics of CMV-specific T cell response and factors associated with high CMV-specific T cell responses 1 year after HCT. In HCT recipients, CMV pp65 and IE1-specific ELISPOT assay were performed before HCT (D0), and at 30 (D30), 90 (D90), 180 (D180), and 360 (D360) days after HCT. Of the 51 HCT recipients with donor-positive (D+)/recipient-positive (R+) serology, 26 (51%) developed CMV infections after HCT. The patterns of post-transplantation reconstitution for CMV-specific T cell response were classified into 4 types: 1) an initial decrease at D30 followed by gradual T cell reconstitution without CMV infection (35%), 2) an initial decrease at D30 followed by gradual T cell reconstitution preceded by CMV infection (35%), 3) failure of gradual or constant T cell reconstitution (26%), and 4) no significant T cell reconstitution (4%). There was no significant difference between ELISPOT counts of D360 and those of D0. High CMV-specific T cell responses at D360 were not associated with high CMV-specific T cell response at D0, CMV infection, ganciclovir therapy, graft versus host disease (GVHD), and immunosuppressant use. In conclusion, there are 4 distinct patterns of reconstitution of the CMV-specific T cell response after HCT. In addition, reconstituted donor-origin CMV-specific T cell responses appeared to be constant until day 360 after HCT, regardless of the level of the pre-transplant CMV-specific T cell response, CMV infection, and immunosuppressant use.

Teofilina como agente capacitante do sêmen bovino / Theophylline as a capacitating agent of bovine semen

Objetivou-se avaliar a teofilina como agente capacitante substituto ou associado à heparina sobre a reação acrossômica dos espermatozoides e o desenvolvimento de embriões produzidos in vitro. O experimento foi realizado com quatro touros e três tratamentos, totalizando 12 grupos experimentais. O sêmen dos touros foi avaliado nos tratamentos descritos a seguir: tratamento 1 (HEP): heparina - 10µg/mL; tratamento 2 (TEO): teofilina - 5mM; tratamento 3 (HEP + TEO): heparina (10µg/mL) + teofilina (5mM), por zero, seis, 12 e 18 horas, corados com trypan blue/Giemsa para avaliação da reação acrossômica. Para a produção dos embriões, os agentes capacitantes foram adicionados aos meios de fertilização. Na análise espermática, a taxa de reação acrossômica verdadeira foi maior (P<0,05) no tempo zero hora, enquanto para espermatozoides mortos, as maiores taxas (P<0,05) foram nos tempos de 12h (84,46±5,82) e 18h (86,75±4,19). A taxa de embriões produzidos (37,97±13) e a taxa de eclosão (33,50±14) foram maiores (P<0,05) para o tratamento HEP. Não foi observada diferença (P>0,05) entre touros na análise de reação acrossômica nem na PIVE. A utilização da teofilina foi tão eficiente quanto a da heparina na indução da reação acrossômica, no entanto resultou em menores taxas de produção embrionária.(AU)

The sperm capacitating process should take special attention during in vitro embryo production (IVEP) once that affects the success of embryo production. The study aimed to evaluate theophylline as substitute capacitating agent or in combination with heparin on the sperm acrosome reaction and development of embryos produced in vitro. The experiment was carried out using 4 bulls and 3 treatments, establishing 12 experimental groups. Each bull was evaluated in the following treatments: Treatment 1 (HEP): Heparin - 10mg/mL; Treatment 2 (THEO): Theophylline - 5mM; Treatment 3 (HEP + THEO), Heparin (10mg/mL) + Theophylline (5mM). The semen of bulls was incubated in each treatment for 0, 6, 12 and 18h, stained with Trypan blue / Giemsa and analyzed by electron microscopy for assessment of acrosome reaction. Using sperm of same bulls, capacitating agents were added to the fertilization media, for IVEP. In sperm analysis, the true acrosome reaction rate was higher (P<0.05) in time 0h, while sperm dead rates were highest (P<0.05) at 12h (84.46±5, 82), and 18h (86.75±4.19). The produced embryos rate (37.97±13) and hatching rate (33.50±14) were larger (P<0.05) for HEP treatment. There was no difference (P>0.05) between bulls in acrosome reaction analysis neither for IVEP. The use of theophylline was as effective as heparin in the induction of the acrosome reaction, although it resulted in lower embryo production rates.(AU)

A Comparison of International Guidelines for Pediatric Asthma Pharmacotherapy

OBJECTIVE: International institutes such as Global institute for Asthma(GINA), KAAACI(Republic of Korea), NHLBI(USA), BTS(UK) and JSA(Japan) have published guidelines for asthma treatment. The aim of this study was to compare the representatives' international guidelines of pharmacotherapy for pediatric asthma. METHODS: The recommendations related to pharmacotherapy for pediatric asthma were extracted from the latest representatives' international guidelines, and comprehensive comparisons were conducted. RESULTS: Major comparison outcomes between international guidelines were evaluated as follows: classification system on severity and pediatric age group, recommendation for inhaled corticosteroid dose, recommendation for pediatric age group of theophylline in mild asthma, and recommendation for pediatric age group of tiotropium in severe asthma. Clinical trials emphasized the adverse effects of theophylline, whereas tiotropium demonstrated beneficial actions for pediatric asthma. Therefore, theophylline was recommended for older patients with persistent asthma, and tiotropium was considered to be suitable for younger patients with severe asthma according to GINA guidelines. CONCLUSION: These findings address the requirement to harmonize international guidelines of pharmacotherapy in pediatric asthma. In addition, the findings suggest that KAAACI needs to update its pharmacotherapy guidelines of theophylline, tiotropium and other medicines recently approved.

Asma grave / Severe asthma

Heterogeneidade é um traço marcante da asma. Síndrome complexa, resulta da interligação de uma rede genética com fatores ambientais, o que gera um comportamento alterado das células estruturais e funcionais do trato respiratório que desemboca em diferentes processos inflamatórios. Como resultado final, distingue-se uma ampla gama de apresentações clínicas e desfechos terapêuticos. Estima-se que 5%-10% dos asmáticos sejam portadores de uma forma grave, caracterizada pelo controle insuficiente da disfunção, apesar do uso de doses elevadas de múltiplos medicamentos. Asmáticos graves têm taxas mais elevadas de idas a serviços de emergência, hospitalizações, absenteísmo e letalidade. Mesmo comprometendo uma parcela menor de pessoas, essa categoria responde pela maior parte dos gastos envolvidos com a asma. Com a identificação progressiva de novos alvos terapêuticos e consequente desenvolvimento de novos medicamentos, é possível que, num futuro próximo, possamos oferecer tratamento efetivo e maior qualidade de vida a essa parcela mais comprometida dos asmáticos.

Heterogeneity is a striking feature of asthma. Asthma is a complex syndrome, in which a link between a genetic network and environmental factors generates altered behavior of structural and functional cells of the respiratory tract that ends in different inflammatory processes. The result is a wide range of clinical presentations and therapeutic outcomes. It is estimated that 5%-10% of those with asthma suffer from a severe form characterized by insufficient control of the dysfunction, despite the use of high doses of multiple drugs. Those with severe asthma have higher rates of visits to the emergency services, hospitalizations, absenteeism and mortality. Despite those with severe asthma representing only a small percentage of the total, this group accounts for most of the expense associated with asthma. With the progressive identification of new therapeutic targets and the consequent development of new drugs, it is possible that in the near future, we can provide more effective treatment and improved quality of life for those with the more severe disease.

Effect of cellulose acetate phthalate and polyethylene glycol on physical properties and release of theophylline from microcapsules

ABSTRACT The present study describes the development of theophylline microcapsules by a non-solvent addition method and the effect of plasticizer addition on microencapsulation. The release was studied in distilled water and the data were analysed by various mathematical models for determining the mechanism of release. Prepared microcapsules were found to be spherical, free flowing and having more than 80% entrapped drug. The polymer - cellulose acetate phthalate and plasticizer - polyethylene glycol was considered to be affecting the properties of microcapsules including drug release (time for 50% drug release, T50). The formulation with the highest proportion of polymer and without plasticizer (F3) showed the slowest release with T50 = 4.3 h, while the formulation with lower proportion of polymer and 20% (w/w) plasticizer (F13 &14) showed the fastest release of drug with T50 values of 1.2 h and 1.3 h, respectively. The drug release from most of the formulations was found to be following Higuchi model. It is concluded from the results of the present study that cellulose acetate phthalate significantly affects the sustained release of the drug in water, whereas the addition of polyethylene glycol slightly enhances the drug release.

RESUMO O presente estudo descreve o desenvolvimento de microcápsulas de teofilina pelo método sem adição de solvente e o efeito da adição de plastificante na microencapsulação. A liberação foi estudada em água destilada e os dados foram analisados por vários modelos matemáticos para determinação do mecanismo de liberação. As microcápsulas preparadas mostraram-se esféricas, livres de corrente e com mais de 80% de fármaco encapsulado. O polímero - ftalato de acetato de celulose e o plastificante - polietileno glicol - afetaram as propriedades das microcápsulas, incluindo a liberação do fármaco (tempo para liberação de 50% do fármaco, T50). A formulação com a maior proporção de polímero e sem plastificante (F3) se mostrou como a de liberação mais lenta, com T50 = 4,3 h, enquanto as formulações com menor proporção de polímero e 20% de plastificante (m/m) (F13 &14) apresentaram a liberação mais rápida do fármaco, com T50 de 1,2 h e 1,3 h, respectivamente. A liberação do fármaco para a maioria das formulações seguiu o modelo de Higuchi. Concluiu-se, dos resultados do presente estudo, que o ftalato do acetato de celulose afeta significativamente a liberação controlada do fármaco em água, enquanto que a adição de polietileno glicol aumenta ligeiramente a liberação do fármaco.

Contribution of water and lipid soluble substances in the relaxant effects of Tymus vulgaris extract on guinea pig tracheal smooth muscle in vitro / 中国结合医学杂志

<p><b>OBJECTIVE</b>To examine the relaxant effects of hydro-ethanolic, macerated aqueous (MA) and lipidfree macerated aqueous (LFMA) extract of Tymus vulgaris on tracheal chains of guinea pigs.</p><p><b>METHODS</b>The relaxant effects of five cumulative concentrations of each extract (0.4, 0.8, 1.2, 1.6 and 2.0 g/100 mL) were compared with saline as negative control and five cumulative concentrations of theophylline (0.1, 0.2, 0.4, 0.6 and 0.8 mmol/L) on precontracted tracheal smooth muscle of guinea pig with 60 mmol/L KCl (group 1) and 10 µmol/L methacholine (group 2, n=6 for each group).</p><p><b>RESULTS</b>In group 1 all concentrations of theophylline, three higher concentrations of hydro-ethanolic, two concentrations of LFMA and last concentration of MA extracts showed significant relaxant effects compared with that of saline (P<0.05 or P<0.01). Two lower concentrations of LFMA and all concentrations of MA except higher one caused contraction compared with saline (P<0.05 or 0.01). In group 2 experiments, all concentrations of theophylline, hydro-ethanolic, MA and LFMA extracts showed significant relaxant effects compared to that of saline (P<0.05 or P<0.01). In both groups, the relaxant effect of all concentrations of hydro-ethanolic extract were significantly higher than most concentrations of others (P<0.05 or P<0.01). The relaxant effect of different concentrations of three extracts were significantly greater in group 2 compared with group 1 experiments (all P<0.01). There were significantly positive correlations between the relaxant effects and concentrations for theophylline and all extracts in both groups (P<0.05 or P<0.01).</p><p><b>CONCLUSION</b>Hydro-ethanolic extract has a potent weaker relaxant effect for other extracts from Tymus vulgaris on tracheal chains of guinea pigs.</p>

The study of anticoagulants selection in platelet-rich plasma preparation / 中华整形外科杂志

<p><b>OBJECTIVE</b>To investigate the effect of the anticoagulants on PRP quality, so as to clarify the appropriate anticoagulant used in PRP production.</p><p><b>METHODS</b>The microstructure change of platelets collected via heparin, citrate, acid citrate dextrose (ACD) and citrate-theophylline-adenosine-dipyridamole ( CTAD) was observed by TEM following time course. The extent of spontaneous activation of platelets in four groups was detected by measuring sP-selectin in plasma. The TGF-β1 release amount of activated PRP of four groups was measured.</p><p><b>RESULTS</b>CTAD is superior to other anticoagulants in maintaining the integrity of platelet structures for a long time and preventing platelet spontaneous activation. ACD slightly surpassed heparin and citrate in above two aspects. ACD-PRP and CTAD-PRP released significantly more TGF-β1 compared with heparin and citrate.</p><p><b>CONCLUSIONS</b>The PRP quality and biological effects were strongly associated with the type of Anticoagulants. ACD and CTAD are optimal anticoagulants in PRP production for they can maintain platelet viability at a high level.</p>

Study of change in activity of hepatic drug metabolism enzymes in rat model of chronic unpredictable mild stress / 药学学报

This study aimed to explore the impact of depression caused by chronic unpredictable mild stress (CUMS) on in vivo activity of six kinds of CYP450 isoforms in rats. According to 'Katz' method, the model of CUMS was established. Tolbutamide, chlorzoxazone, theophylline, midazolam, omeprazole and dextromethorphan were chosen as probe substrates of CYP2C6, CYP2E1, CYP1A2, CYP3A2, CYP2D1 and CYP2D2 of rats. Plasma concentration of six kinds of CYP450 in control group and model group were determined by LC-MS/MS and computed pharmacokinetic parameters. Consequently, metabolism of theophylline and chlorzoxazone accelerated significantly (P < 0.01), but tolbutamide, dextromethorphan, omeprazole and midazolam had no significant difference. The present study proved that depression caused by CUMS had strong induction to CYP1A2 and medium induction to CYP2E1.

Comparison between Caffeine and Theophylline Therapy for Apnea of Prematurity

PURPOSE: Methylxanthines are commonly used to treat apnea of prematurity. Recent studies have reported that caffeine therapy reduces the rate of bronchopulmonary dysplasia (BPD) and improves the rate of survival in preterm infant without neurodevelopmental disabilities. This study was performed to compare the effects on apnea episodes, adverse effects and morbidity between the caffeine and theophylline groups. METHODS: A retrospective study was performed in 143 infants born at less than 33 weeks of gestation and treated with caffeine (n=54) or theophylline (n=89) from 2011 to 2012. The baseline characteristics of mothers and their infants were examined. The number of apnea events before and after treatment, the duration of respiratory support, and the rate of re-intubation were compared. Furthermore, adverse effects, clinical course, and morbidities such as BPD and periventricular leukomalacia were compared before discharge. RESULTS: There were no significant differences in the baseline characteristics. Theophylline and caffeine appeared to have similar short-term therapeutic advantages on apnea of prematurity in mean apnea rate after first two weeks of treatment. However, there were no statistically significant differences in the duration of respiratory support, rate of re-intubation, clinical course, and morbidity between the two groups. Adverse effects, indicated by feeding intolerance were lower in the caffeine group. CONCLUSION: Caffeine was as effective as theophylline in the short-term for reducing apnea in preterm babies and was better tolerated and was easier to administer. A prospective randomized study is needed to confirm the effect of caffeine on the lone-term neurodevelopmental outcome in prematurity.

Quantitative analysis of theophylline and its metabolites in urine of Chinese healthy subjects after oral administration of theophylline sustained-release tablets / 药学学报

To study the metabolite excretion of theophylline, a rapid and specific method by liquid chromatography with heated electrospray ionization tandem mass spectrometry (LC-HESI/MS/MS) method for simultaneous determination of theophylline, 1, 3-dimethyluric acid (1,3-DMU), 3-methylxanthine (3-MX) and 1-methyluric acid (1-MU) in human urine was developed using theophylline-d6 and 5-fluorouracil as internal standards. Selected reaction monitoring (SRM) with heated electrospray ionization (HESI) was used in the negative mode for mass spectrometric detection. After diluted with methanol and centrifuged, the analytes and ISs were separated on a XDB-Phenyl (150 mm x 4.6 mm, 5 microm) column with a mixture of water-methanol-formic acid (30 : 70 : 0.15) as mobile phase at a flow rate of 0.6 mL x min(-1). The linear calibration curves for theophylline, 1, 3-DMU, 3-MX and 1-MU were obtained in the concentration range of 1.0-250 microg x mL(-1), separately. The method herein described is effective and convenient, and can be used for determination of theophylline and its three metabolites. The results showed that urinary excretion ratio of theophylline, 1,3-DMU, 3-MX and 1-MU is approximately 1 : 3 : 1 : 2 in Chinese subjects, which is similar to the reported excretion pattern in Caucasian.