Novel frameshift mutation in the CHD7 gene associated with CHARGE syndrome with preaxial polydactyly

We report a male patient with multiple congenital anomalies, including coloboma, Fallot tetralogy, bilateral choanal atresia, dysmorphic features (low set malformed ears, fronto-maxillary facial angle deviation, hypertelorism, retrognathism), micropenis, preaxial polydactyly and ureter stenosis. The major abnormalities had been diagnosed in prenatal period by ultrasound examination and the clinical diagnosis of CHARGE syndrome was established in postnatal periode by sequence analysis of the CHD7 coding region pointing to a novel heterozygous 4-basepair deletion in exon 3 that leads to an early stop codon and truncated CHD7 protein. Based on previous literature reports this is the first case of CHARGE syndrome with preaxial polydactyly characterized by this frameshift mutation. This case report allows further delineation of CHARGE syndrome polymorphism

Fungaemia caused by Candida pulcherrima

Although neonatal bloodstream infections may be caused by a variety of fungi, invasive fungaemia due to Candida pulcherrima in a premature neonate has not been previously reported. We describe such a case in which antifungal susceptibility test data led to successful therapy. A colonized catheter used for parenteral nutrition is presumed to have been the main source of this persistent infection. © 2012 ISHAM

Cellular electrophysiological effect of terikalant in the dog heart

The cellular mechanism of action of terikalant, an investigational antiarrhythmic agent known to block the inward rectifier and other potassium currents, has not yet been fully clarified. The aim of the present study was therefore to analyse the in vitro electrophysiological effects of terikalant in canine isolated ventricular muscle and Purkinje fibers by applying the standard microelectrode technique. The effects of terikalant on the duration of action potential at a stimulation cycle length of 1000 ms and on the maximum upstroke velocity of the action potential in right ventricular papillary muscle were examined at 1, 2.5, 10, and 20 mu M concentrations. Terikalant significantly prolonged the action potential duration measured both at 50% and 90% of repolarization in concentration-dependent manner. The maximum upstroke velocity of the action potential was unaffected at 1 and 2.5 mu M concentrations. However, this parameter was significantly reduced at 10 and 20 mu M concentrations of terikalant. In Purkinje fibers terikalant (2.5 mu M) also produced a marked action potential lengthening effect. Frequency dependence (cycle length of 300-5000 ms) of the action potential lengthening effect of terikalant was studied at a concentration of 2.5 mu M. Prolongation of the duration of action potential occurred in a reverse frequency-dependent manner both in papillary muscle and Purkinje fibers, with a more pronounced frequency-dependence observed in Purkinje fibers. The onset kinetics of the terikalant (10 mu M) induced block of the maximum upstroke velocity of the action potential was rapid (0.6 +/- 0.1 beat(-1) n=6) like that of Class I/B antiarrhythmics, and the offset (recovery) kinetics of the drug (2956 696 ms, n=6) best resembled that of Class I/A antiarrhythmic drugs. It was concluded that terikalant, unlike pure Class III antiarrhythmic drugs, has combined mode of action by lengthening repolarization and blocking the inward sodium current in a use-dependent manner

Effects of Chelidonium majus extracts and major alkaloids on hERG potassium channels and on dog cardiac action potential - a safety approach

Chelidonium majus or greater celandine is spread throughout the world, and it is a very common and frequent component of modern phytotherapy. Although C. majus contains alkaloids with remarkable physiological effect, moreover, safety pharmacology properties of this plant are not widely clarified, medications prepared from this plant are often used internally. In our study the inhibitory effect of C. majus herb extracts and alkaloids on hERG potassium current as well as on cardiac action potential were investigated. Our data show that hydroalcoholic extracts of greater celandine and its alkaloids, especially berberine, chelidonine and sanguinarine have significant hERG potassium channel blocking effect. These extracts and alkaloids also prolong the cardiac action potential in dog ventricular muscle. Therefore these compounds may consequently delay cardiac repolarization, which may result in the prolongation of the QT interval and increase the risk of potentially fatal ventricular arrhythmias