There has been widespread interest surrounding the use of beta-blockers (i.e. propranolol, timolol, nadolol, acebutolol) in the treatment of infantile hemangiomas (IH).To review literature evaluating treatment of IH with propranolol.We conducted a literature search on PubMed and investigated for case reports, case series, and controlled trials by using search terms including hemangioma and propranolol. RESUltS: Data suggest that beta-blockers are efficacious in cutaneous, orbital, subglottic, and hepatic hemangiomas and assist in the resolution of ulcerated hemangiomas. Improvement has also been documented in children with PHACE syndrome. Propranolol produces favorable results in children who do not respond to steroids and with no long-term adverse effects. Propranolol should be administered with caution due to rare but serious side effects including hypoglycemia, wheezing, hypotension, and bradycardia. Additionally, recurrence of lesions following the cessation of treatment has been documented.Although large-scale randomized controlled trials must be conducted in order to further evaluate the safety and the possible role of propranolol in the treatment of IH, the reviewed literature suggests that propranolol carries promise as a potential replacement for corticosteroids as first-line therapy or as a part of a multimodal approach.

OBJECTIVES:

Systematic review of preventive pharmacologic treatments for community-dwelling adults with episodic migraine.

DATA SOURCES:

Electronic databases through May 20, 2012. ELIGIBILITY CRITERIA: English-language randomized controlled trials (RCTs) of preventive drugs compared to placebo or active treatments examining rates of ≥50 % reduction in monthly migraine frequency or improvement in quality of life. STUDY APPRAISAL AND SYNTHESIS

METHODS:

We assessed risk of bias and strength of evidence and conducted random effects meta-analyses of absolute risk differences and Bayesian network meta-analysis.

RESULTS:

Of 5,244 retrieved references, 215 publications of RCTs provided mostly low-strength evidence because of the risk of bias and imprecision. RCTs examined 59 drugs from 14 drug classes. All approved drugs, including topiramate (9 RCTs), divalproex (3 RCTs), timolol (3 RCTs), and propranolol (4 RCTs); off-label beta blockers metoprolol (4 RCTs), atenolol (1 RCT), nadolol (1 RCT), and acebutolol (1 RCT); angiotensin-converting enzyme inhibitors captopril (1 RCT) and lisinopril (1 RCT); and angiotensin II receptor blocker candesartan (1 RCT), outperformed placebo in reducing monthly migraine frequency by ≥50 % in 200-400 patients per 1,000 treated. Adverse effects leading to treatment discontinuation (68 RCTs) were greater with topiramate, off-label antiepileptics, and antidepressants than with placebo. Limited direct evidence as well as frequentist and exploratory network Bayesian meta-analysis showed no statistically significant differences in benefits between approved drugs. Off-label angiotensin-inhibiting drugs and beta-blockers were most effective and tolerable for episodic migraine prevention.

LIMITATIONS:

We did not quantify reporting bias or contact principal investigators regarding unpublished trials.

CONCLUSIONS:

Approved drugs prevented episodic migraine frequency by ≥50 % with no statistically significant difference between them. Exploratory network meta-analysis suggested that off-label angiotensin-inhibiting drugs and beta-blockers had favorable benefit-to-harm ratios. Evidence is lacking for long-term effects of drug treatments (i.e., trials of more than 3 months duration), especially for quality of life.

Capillary columns were packed firstly with silica modified-teicoplanin (teico-CSP) particles for a short zone (1-5 cm) and then with a Cogent Bidentate C18 silica phase (25 cm). The first part of the column (inlet) was intended for focusing the sample model, consisted of selected basic compounds, while the second zone, containing RP18 particles, was used for their separation. For method optimization, some important experimental parameters were studied including the sample solvent, injected volume and teico-CSP particles length. 3 cm teico-CSP resulted to be effective for the on-line pre-concentration, before the separation, of acebutolol, alprenolol, nadolol, oxprenolol and terbutaline with limit of detection at levels of few ng/mL. The comparison of the data obtained in absence of the chiral stationary phase revealed that the use of this chiral short sector into the capillary allowed the increase of the sensitivity of 5-12 times. Injection of larger sample volumes were easily done using higher length of the teico-CSP into the capillary, however the use of 5 cm length was not appropriate because caused the partial chiral separation of some studied compounds.

A simple and sensitive liquid chromatography-tandem mass spectrometry method was developed and validated in rat plasma for quantification of tadalafil, a novel therapeutic agent for erectile dysfunction. Tadalafil and acebutolol (internal standard) were extracted by liquid-liquid extraction with tert-butyl methyl ether. The chromatographic separation was performed on a reverse phase C18 column with a mobile phase consisting of 0.1 % formic acid and acetonitrile (45:55, v/v) at a flow rate of 0.3 mL/min. The protonated analyte was quantitated by multiple reaction monitoring with a Waters Quattro micro™ API mass spectrometer. The calibration curve was linear over a concentration range of 2-2000 ng/mL, and the lower limit of quantification was 2 ng/mL with a precision (CV %) of 10.9 %. Acceptable intra-day and inter-day precision and accuracy were obtained at 3 concentration levels (3, 200, and 1500 ng/mL). Tadalafil was found to be stable in a battery of studies, including bench top, freeze-thaw, and autosampler conditions. The validated method was successfully used to determine tadalafil concentration in rat plasma samples after oral administration at a dose of 1 mg/kg.

The coupling between an electrochemical cell (EC) and a mass spectrometer (MS) is a useful screening tool (EC-MS) to study the oxidative transformation pathways of various electroactive species. For that purpose, we showed that the EC-MS method, carried out in the presence and absence of isotope (18)O labeled water leads not only to a fast identification of oxidation products but also leads to a fast elucidation of the mechanism pathway reaction. We examined herein the case of the electrochemical hydrolysis of activated aromatic ether. Acebutolol (β-blockers) was selected herein as model of activated aromatic ether, and its electrochemical oxidation was examined in both the presence and absence of isotope (18)O labeled water. To elucidate electrochemical hydrolysis pathway reaction: O-dealkylation or O-dealkoxylation, our approach was used to prove its applicability. The electrochemical oxidation mechanism was then elucidated showing an O-dealkoxylation reaction. In addition, density functional theory (DFT) calculations fully support the experimental conclusions.

The interaction of propranolol and acebutolol with biological membranes was assessed in the present work by using a range of biophysical techniques and liposomes, as membrane mimetic models. Liposomes were made of zwitterionic phosphatidylcholines and experiments were performed at physiologic pH and at various membrane physical states (gel, ripple and fluid phases). Fluorescence techniques were used to study the partition coefficient of β-blockers, the influence of drugs on membrane fluidity and the drugs-membrane binding. Moreover, small and wide angle X-ray scattering techniques were used to evaluate the β-blockers effect on long range bilayer order and hydrocarbon chain packing. The gathered results highlighted the importance of electrostatic interactions between propranolol and acebutolol with membranes. Furthermore, both β-blockers exhibited a membrane-fluidizing effect and the capacity to disturb the membrane organization. In general, propranolol unveiled a more pronounced effect on membrane fluidity and structure than acebutolol. In the current study, the obtained results were also correlated with the cardioprotective properties of the β-blockers studied.

A highly sensitive method for simultaneous determinations of eleven β-blockers and β-agonists in distilled and waste-waters using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS-MS) was developed, optimized and validated. The method was used for trace determinations of acebutolol, atenolol, metoprolol, propranolol, timolol, nadolol, labetalol, oxprenolol, pindolol, alprenolol and terbutaline. Oasis MCX and Clean Screen cartridges were used for solid phase extractions and an alkaline mixture of dichloromethane-propanol was used as mobile phase. Matrix effect was reduced by using methanol as a pre-eluant for removing co-extractives on the SPE cartridges and by applying the internal standard method for quantification. Using Oasis MCX-SPE cartridges, developed method gave average recoveries of 77.20-97.30% for drugs spiked at 150.00-500.00pg/ml. Intra-day precisions gave RSD of 3.367-12.489% while as inter-day precisions gave RSD of 6.425-19.768%. Detection limits of 0.11-6.74pg/ml and quantification limits of 0.14-22.88pg/ml were obtained. Signal's suppression in the range of 4.50-24.50% was recorded due to the matrix effect. Drugs spiked in wastewater at 500.00pg/ml concentrations level and stored at 4°C for 6 days, showed insignificant degradation. Developed method was successfully applied to the analysis of pharmaceutical residues in effluents wastewaters. Five β-blockers and one β-agonists were detected in Al-Ain and Abu Dhabi wastewaters at average concentrations of 3.44-19.05pg/ml. Atenolol was detected at higher average concentration ranged in 125.60-234.28pg/ml. Results obtained suggest that adopted wastewater treatment processes are not enough to degrade these compounds.

Background Postthoracic surgery atrial fibrillation (AF) is the most frequently occurring arrhythmia. Strategies for preventing AF have been amply evaluated, but currently there are no clearly defined guidelines for treatment of AF after thoracic surgery.Methods The study was prospective and randomized controlled trial. Acebutolol and diltiazem versus placebo were compared, among 117 patients postpneumonectomy or lobectomy at the Thoracosurgery Clinic, Poznan University of Medical Sciences in Poland. Patients who were enrolled in the study were randomly assigned to one of the three groups: those who received acebutolol (Group 1) or diltiazem (Group 2) and compared with patients without antiarrhythmic drugs (Group 0). Each group consisted of 39 patients. The patients were continuously monitored postoperatively with 24 ECG (Holter monitor) in the intensive care unit.Results In patients receiving acebutolol AF occurred in 5% compared with 23% of patients receiving diltiazem and 20% of patients receiving placebo (difference not statistically significant).Conclusions Acebutolol and diltiazem appear to have been non-effective for the treatment or prevention of AF. Side effects were mild. In comparison to diltiazem, however, acebutolol had a beneficial effect on the circulatory system. Patients who had received acebutolol proved to have had fewer tachycardia episodes and supraventricular ectopy during the postoperative period. It seems that acebutolol can be useful, especially in patients with sympathetic activity dominance.

We report a severe case of travellers' diarrhoea in a patient returning from Ecuador to Italy with the concomitant presence of Aeromonas veronii biovar sobria and Vibrio parahaemolyticus in their faeces. Based on diagnostic results, epidemiological information and the clinical outcome, we conclude that the real aetiological agent was A. veronii biovar sobria, while V. parahaemolyticus was only transient in the intestine of the patient.

A new method of analysis has been developed and validated for the determination of plasma celiprolol concentration. Plasma samples (1 ml) were pre-purified by solid-phase extraction with Bond Elut C18. The separation was achieved with XBridge C18 column (150 mm × 3.0mm i.d., 3.5 μm) at 35 °C using a mixture of acetonitrile and 10mM ammonium acetate buffer (pH 10.5) (34:66, v/v) under isocratic conditions at a flow rate of 0.4 ml/min. The peak was detected using a fluorescence detector at excitation 250 nm and emission 482 nm. Retention times for the internal standard (acebutolol) and celiprolol were 4.2 min and 6.3 min, respectively. Calibration curves were linear over the range of 1.0-1000 ng/ml (r>0.999), with a limit of quantification at 1.0 ng/ml. Intra- and inter-assay precision (relative standard deviation) were less than 13.3% and the accuracy (relative error) was -5.1% to 11.5% at four different concentrations. This proposed method was successfully applied to a study of pharmacokinetic interactions between celiprolol and apple juice in humans.