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Chemistry Central Journal Feb 2012A validated simple, rapid, sensitive and specific square-wave voltammetric technique is described for the determination of acebutolol (AC) following its accumulation...
A validated simple, rapid, sensitive and specific square-wave voltammetric technique is described for the determination of acebutolol (AC) following its accumulation onto a hanging mercury drop electrode in a Britton-Robinson universal buffer of pH 7.5. The optimal procedural conditions were: accumulation potential Eacc = - 0.8 V versus Ag/AgCl/KCl, accumulation duration tacc = 30 s, pulse-amplitude = 70 mV, scan rate = 100 mV/s, frequency = 30 Hz, surface area of the working electrode = 0.6 mm2 and the convection rate = 2000 rpm. Under these optimized conditions, the adsorptive stripping voltammetry (AdSV) peak current was proportional over the concentration range 5 × 10-7 - 6 × 10-6 M (r = 0.999). Recoveries for acebutolol from human plasma and urine were in the range 97-103% and 96-104% respectively. The method proved to be precise (intra-day precision expressed as %RSD in human plasma ranged from 2.9 - 3.2% and inter-day precision expressed as %RSD ranged from 3.4 - 3.8%) and accurate (intra-day accuracies expressed as % error in human urine ranged from -3.3 - 2.8% and inter-day accuracies ranged from -3.3 - 1.7%). The limit of quantitation (LOQ) and limit of detection (LOD) for acebutolol were 1.7 × 10-7 and 5 × 10-7 M, respectively. Possible interferences by substances usually present in the pharmaceutical formulations were investigated with a mean recovery of 101.6 ± 0.64%. Results of the developed square-wave adsorptive stripping voltammetry (SW-AdSV) method were comparable with those obtained by reference analytical method.
PubMed: 22353684
DOI: 10.1186/1752-153X-6-15 -
Molecular Biology and Evolution Jun 2012The human ZC3HAV1 gene encodes an antiviral protein. The longest splicing isoform of ZC3HAV1 contains a C-terminal PARP-like domain, which has evolved under positive...
The human ZC3HAV1 gene encodes an antiviral protein. The longest splicing isoform of ZC3HAV1 contains a C-terminal PARP-like domain, which has evolved under positive selection in primates. We analyzed the evolutionary history of this same domain in humans and in Pan troglodytes. We identified two variants that segregate in both humans and chimpanzees; one of them (rs3735007) does not occur at a hypermutable site and accounts for a nonsynonymous substitution (Thr851Ile). The probability that the two trans-specific polymorphisms have occurred independently in the two lineages was estimated to be low (P = 0.0054), suggesting that at least one of them has arisen before speciation and has been maintained by selection. Population genetic analyses in humans indicated that the region surrounding the shared variants displays strong evidences of long-standing balancing selection. Selection signatures were also observed in a chimpanzee population sample. Inspection of 1000 Genomes data confirmed these findings but indicated that search for selection signatures using low-coverage whole-genome data may need masking of repetitive sequences. A case-control study of more than 1,000 individuals from mainland Italy indicated that the Thr851Ile SNP is significantly associated with susceptibility to multiple sclerosis (MS) (odds ratio [OR] = 1.47, 95% confidence intervals [CI]: 1.08-1.99, P = 0.011). This finding was confirmed in a larger sample of 4,416 Sardinians cases/controls (OR = 1.18, 95% CI: 1.037-1.344, P = 0.011), but not in a population from Belgium. We provide one of the first instances of human/chimpanzee trans-specific coding variant located outside the major histocompatibility complex region. The selective pressure is likely to be virus driven; in modern populations, this variant associates with susceptibility to MS, possibly via the interaction with environmental factors.
Topics: Acebutolol; Animals; Case-Control Studies; Gene-Environment Interaction; Genetic Association Studies; Genetic Predisposition to Disease; Genome, Human; Haplotypes; Humans; Linkage Disequilibrium; Models, Genetic; Multiple Sclerosis; Odds Ratio; Pan troglodytes; Phylogeny; Polymorphism, Single Nucleotide; Protein Isoforms; Protein Structure, Tertiary; RNA-Binding Proteins; Selection, Genetic; Sequence Analysis, DNA
PubMed: 22319148
DOI: 10.1093/molbev/mss002 -
The American Journal of Cardiology Apr 2012The aim of this study was to assess exercise test results and efficacy of therapy with a β blocker (acebutolol) in ryanodine receptor type 2 (RyR2) mutation carriers... (Comparative Study)
Comparative Study
The aim of this study was to assess exercise test results and efficacy of therapy with a β blocker (acebutolol) in ryanodine receptor type 2 (RyR2) mutation carriers with documented ventricular arrhythmias (VAs) and long-term follow-up. Twenty RyR2 mutation carriers belonging to 8 families and regularly followed at our center were analyzed using a study protocol involving electrocardiography, exercise tests off and on β-blocker therapy, 2-dimensional echocardiography, and signal-averaged electrocardiography. Off-therapy exercise testing triggered the onset of VAs at different heart rates (mean 132 ± 13 beats/min) with various patterns that worsened while exercising and disappeared immediately after stopping. The most severe VAs detected were nonsustained ventricular tachycardia in 35% and ventricular couplets in 35%. In the remaining subjects single ventricular premature beats were recorded. In 15% of patients single monomorphic ventricular premature beats were detected and identified to be linked to RyR2 mutations owing to the presence of sudden deaths of their family members and subsequent family screening. Acebutolol made the VAs disappear completely in 20% of subjects and decreased their complexity in 50%, whereas it did not change VAs appreciably in 30% of patients with less complex VAs. After 11 ± 8 years of follow-up 2 patients developed syncope. In conclusion, exercise testing was a fundamental tool for assessing the clinical phenotype and efficacy of therapy in RyR2 mutation carriers and therapy with acebutolol led in most subjects to a decreased complexity of the arrhythmic pattern or to complete suppression.
Topics: Acebutolol; Adolescent; Adult; Anti-Arrhythmia Agents; Cohort Studies; Death, Sudden, Cardiac; Echocardiography; Electrocardiography; Exercise Test; Family; Female; Follow-Up Studies; Genetic Markers; Genetic Testing; Heterozygote; Humans; Male; Mutation; Pedigree; Phenotype; Physical Exertion; Ryanodine Receptor Calcium Release Channel; Tachycardia, Ventricular; Treatment Outcome
PubMed: 22221940
DOI: 10.1016/j.amjcard.2011.11.033 -
Journal of Nutritional Science and... 2011Selenocysteine lyase (SCL) catalyzes the decomposition of L-selenocysteine to yield L-alanine and selenium by acting exclusively on l-selenocysteine. The X-ray...
Selenocysteine lyase (SCL) catalyzes the decomposition of L-selenocysteine to yield L-alanine and selenium by acting exclusively on l-selenocysteine. The X-ray structural analysis of rat SCL has demonstrated how SCL discriminates L-selenocysteine from L-cysteine on the molecular basis. SCL has been proposed to function in the recycling of the micronutrient selenium from degraded selenoproteins containing selenocysteine residues, but the role of SCL in selenium metabolism in vivo remains unclear. We here demonstrate that the (75)Se-labeling efficiency of selenoproteins with (75)Se-labeled selenoprotein P (Sepp1) as a selenium source was decreased in HeLa cells transfected with SCL siRNA as compared to the cells transfected with control siRNA. Immunocytochemical analyses showed high SCL expression in kidney and liver cells, where selenocysteine is recovered from selenoproteins. Mature testes of mice exhibited a specific staining pattern of SCL in spermatids that actively produce selenoproteins. However, SCL was weakly expressed in Sertoli cells, which receive Sepp1 and supply selenium to germ cells. These demonstrate that SCL occurs in the cells requiring selenoproteins, probably to recycle selenium derived from selenoproteins such as Sepp1.
Topics: Acebutolol; Animals; HeLa Cells; Humans; Isotope Labeling; Kidney; Liver; Lyases; Male; Mice; RNA, Small Interfering; Rats; Selenium; Selenocysteine; Selenoprotein P; Selenoproteins; Sertoli Cells; Spermatids; Substrate Specificity; Transfection
PubMed: 22041913
DOI: 10.3177/jnsv.57.298 -
European Annals of Otorhinolaryngology,... Nov 2011Infantile haemangioma (IH) is the most common tumour during early childhood. Although these benign lesions resolve spontaneously, up until recently laryngotracheal sites... (Review)
Review
Infantile haemangioma (IH) is the most common tumour during early childhood. Although these benign lesions resolve spontaneously, up until recently laryngotracheal sites of IH required invasive management. The dramatic efficacy of β-blockers on IH has radically changed the prognosis. Surgery is now no longer indicated as first-line therapy, but should only be performed for difficult, refractory cases, or in the presence of absolute contraindications to β-blockers. Long-term steroid therapy is also no longer indicated. Propranolol can be used as first-line, single-agent therapy.
Topics: Acebutolol; Adrenergic beta-Antagonists; Dose-Response Relationship, Drug; Hemangioma; Humans; Infant; Laryngeal Neoplasms; Laryngoscopy; Propranolol; Tracheal Neoplasms
PubMed: 21498145
DOI: 10.1016/j.anorl.2010.11.009 -
British Journal of Clinical Pharmacology Nov 2010A new type of interaction in which fruit juices diminish oral drug bioavailability through inhibition of uptake transport is the focus of this review. The discovery was... (Review)
Review
A new type of interaction in which fruit juices diminish oral drug bioavailability through inhibition of uptake transport is the focus of this review. The discovery was based on an opposite to anticipated finding when assessing the possibility of grapefruit juice increasing oral fexofenadine bioavailability in humans through inhibition of intestinal MDR1-mediated efflux transport. In follow-up investigations, grapefruit or orange juice at low concentrations potentially and selectively inhibited in vitro OATP1A2-mediated uptake compared with MDR1-caused efflux substrate transport. These juices at high volume dramatically depressed oral fexofenadine bioavailability. Grapefruit was the representative juice to characterize the interaction subsequently. A volume-effect relationship study using a normal juice amount halved average fexofenadine absorption. Individual variability and reproducibility data indicated the clinical interaction involved direct inhibition of intestinal OATP1A2. Naringin was a major causal component suggesting that other flavonoids in fruits and vegetables might also produce the effect. Duration of juice clinical inhibition of fexofenadine absorption lasted more than 2 h but less than 4 h indicating the interaction was avoidable with appropriate interval of time between juice and drug consumption. Grapefruit juice lowered the oral bioavailability of several medications transported by OATP1A2 (acebutolol, celiprolol, fexofenadine, talinolol, L-thyroxine) while orange juice did the same for others (atenolol, celiprolol, ciprofloxacin, fexofenadine). Juice clinical inhibition of OATP2B1 was unresolved while that of OATP1B1 seemed unlikely. The interaction between grapefruit juice and etoposide also seemed relevant. Knowledge of both affected uptake transporter and drug hydrophilicity assisted prediction of the clinical interaction with grapefruit or orange juice.
Topics: Administration, Oral; Anti-Allergic Agents; Beverages; Biological Availability; Citrus; Citrus paradisi; Food-Drug Interactions; Histamine H1 Antagonists, Non-Sedating; Humans; Organic Anion Transporters; Terfenadine
PubMed: 21039758
DOI: 10.1111/j.1365-2125.2010.03722.x -
Journal of Pharmaceutical Sciences Jul 2009Gastrointestinal absorption of several beta-blockers is inhibited by citrus juices, although molecular mechanism(s) lying on their small intestinal absorption has not...
Gastrointestinal absorption of several beta-blockers is inhibited by citrus juices, although molecular mechanism(s) lying on their small intestinal absorption has not yet been identified. Here, we attempted to demonstrate involvement of both influx and efflux transporters in vivo in gastrointestinal absorption of celiprolol in mice. Plasma concentration of celiprolol (3 mg/kg) after oral administration was mostly under the limit of quantification in wild mice, whereas that in mdr1a/b knockout (mdr1a/b(-/-)) mice was much more obvious, indicating P-glycoprotein-mediated efflux. Then, the oral absorption of celiprolol in mdr1a/b(-/-) mice was further examined to investigate influx transport mechanism with avoiding effect of P-glycoprotein. Coadministration of bromosulfophthalein (BSP), an inhibitor of various influx transporters including organic anion transporting polypeptide (OATP) reduced plasma celiprolol concentration. Inhibition by BSP of celiprolol uptake from apical membranes was confirmed in Ussing-type chamber of small intestinal tissues. Uptake of celiprolol by human small intestinal transporter OATP-A/1A2 was also confirmed in Xenopus Laevis oocytes. Interestingly, OATP-A/1A2 accepts various beta-blockers including acebutolol, atenolol and sotalol, oral absorption of which is inhibited by coadministration of citrus juice or telithromycin in human. Taken together, these findings have suggested fundamental role of influx transport system(s) in oral absorption of celiprolol.
Topics: ATP Binding Cassette Transporter, Subfamily B, Member 1; Administration, Oral; Adrenergic beta-Antagonists; Animals; Celiprolol; Humans; Intestinal Absorption; Intestine, Small; Male; Mice; Mice, Knockout; Oocytes; Organic Anion Transporters; Sulfobromophthalein; Transfection; Xenopus laevis
PubMed: 19067419
DOI: 10.1002/jps.21618 -
Sensors (Basel, Switzerland) Dec 2007The construction and general performance characteristics of two novelpotentiometric membrane sensors responsive to the acebutolol are described. Thesensors are based on...
The construction and general performance characteristics of two novelpotentiometric membrane sensors responsive to the acebutolol are described. Thesensors are based on the use of ion-association complexes of acebutolol (AC) withtetraphenylborate(TPB) (I) and phosphomolybdate(PM) (II) as exchange sites in a PVCmatrix. The sensors show a fast, stable and near- Nernstian for the mono charge cationof AC over the concentration range 1×10 - ~10 M at 25 °C over the pH range 2.0 -6.0 with cationic slope of 51.5 ± 0.5 and 53.0 ± 0.5 per concentration decade for AC-Iand AC-II sensors respectively. The lower detection limit is 6×10 M and 4×0 M withthe response time 20-30 s in the same order of both sensors. Selectivity coefficients ofAC related to a number of interfering cation and some organic compounds wereinvestigated. There are negligible interferences are caused by most of the investigatedspecies. The direct determination of 3 - 370 μg/ml of AC shows an average recovery of 99.4 and 99.5% and a mean relative standard deviation of 1 . 5 % at 100.0 μg/ml forsensor I and II respectively. The results obtained by determination of AC in tablets usingthe proposed sensors which comparable favorably with those obtained by the Britishpharmacopoeia method. In the present investigation the electrodes have been utilized asend point indicator for some precipitation titration reactions.
PubMed: 28903293
DOI: 10.3390/s7123272 -
Chemical & Pharmaceutical Bulletin Jul 2006A spectrofluorimetric method was described for the determination of drugs containing active methylene groups adjacent to carbonyl groups. The method was applied...
A spectrofluorimetric method was described for the determination of drugs containing active methylene groups adjacent to carbonyl groups. The method was applied successfully to the determination of three life saving cardiovascular drugs, with narrow therapeutic indices: pentoxifylline (I), propafenone hydrochloride (II) and acebutolol hydrochloride (III), in laboratory-prepared mixtures, in commercial tablets and in plasma samples. The method involved the reaction of each of the tested drugs with N1-methyl nicotinamide chloride (NMNCl) in the presence of alkali, followed by addition of formic acid, where highly fluorescent reaction products were produced. The produced fluorescence were measured quantitatively at 472 nm (lambdaex 352 nm), 409 nm (lambdaex 310 nm) and 451 nm (lambdaex 266 nm) for (I), (II), and (III) respectively. The method was linear over concentration ranges of 10-1000 microg/ml , 0.2-12 microg/ml and 0.08-10 microg/ml in standard solutions for (I), (II), and (III) respectively. In spiked human plasma samples, calibration graphs were linear over concentration ranges of 20-1000 microg/ml, 0.2-15 microg/ml and 0.08-10 microg/ml for (I), (II), and (III) respectively. The method showed good accuracy, specificity and precision in both laboratory-prepared mixtures and spiked human plasma samples. The proposed method is simple, with low instrumentation requirements, suitable for quality control application, bioavailability and bioequivalency studies.
Topics: Acebutolol; Fluorescent Dyes; Methane; Niacinamide; Pentoxifylline; Pharmaceutical Preparations; Propafenone; Spectrometry, Fluorescence
PubMed: 16819224
DOI: 10.1248/cpb.54.1026 -
Biological & Pharmaceutical Bulletin Apr 2006The purpose of this study is to characterize transport of acebutolol through the corneal epithelium. Cultured normal rabbit corneal epithelial cells (RCEC) were used to...
The purpose of this study is to characterize transport of acebutolol through the corneal epithelium. Cultured normal rabbit corneal epithelial cells (RCEC) were used to investigate the drug transport. Primary RCEC were seeded on a filter membrane of Transwell-COL insert coated with fibronectin and were grown in Dulbecco's modified Eagle's medium/nutrient mixture F-12 with various supplements. Measurements of acebutolol permeability through RCEC layer were carried out to assess transcellular permeability coefficient (P(transcell)) in the absence or presence of inhibitors. Paracellular permeability coefficient (P(paracell)) was calculated by permeability coefficient of hydrophilic drugs (P(cell)). The transcellular permeability of acebutolol from apical side to basal side (A-to-B) showed concentration-dependency. The acebutolol flux in the A-to-B direction was smaller than that of opposite direction. Sodium azide, verapamil, and cyclosporin A enhanced the transcellular permeability of acebutolol in the A-to-B direction. Acebutolol permeability through an excised rabbit cornea was also increased by verapamil. Thus, it was suggested that acebutolol was actively secreted via P-glycoprotein in a corneal epithelium.
Topics: Acebutolol; Adrenergic beta-Antagonists; Algorithms; Animals; Cells, Cultured; Epithelium, Corneal; In Vitro Techniques; Permeability; Rabbits
PubMed: 16595934
DOI: 10.1248/bpb.29.846