Quinidine Polygalacturonate

Polysaccharide acid (PSA) based devices (consisting of alginic acid and polygalacturonic acid) were investigated for the detection of contaminating microorganisms. PSA-CaCl(2) hydrogel systems were compared to systems involving covalent cross-linking of PSA with glycidylmethacrylate (PSA-GMA) which was confirmed with Fourier Transformed Infrared (FTIR) analysis. Incubation of PSA-CaCl(2) and PSA-GMA beads loaded with Alizarin as a model ingredient with trigger enzymes (polygalacturonases or pectate lyases) or bacteria lead to a smoothening of the surface and exposure of Alizarin according to Environmental Scanning Electron Microscopy (ESEM) analysis. Enzyme triggered release of Alizarin was demonstrated for a commercial enzyme preparation from Aspergillus niger and with purified polygalacturonase and pectate lyase from S. rolfsii and B. pumilus, respectively. In contrast to the PSA-CaCl(2) beads, cross-linking (PSA-GMA beads) restricted the release of Alizarin in absence of enzymes. There was a linear relation between release of Alizarin (5-348 μM) and enzyme activity in a range of 0-300 U ml(-1) dosed. In addition to enzymes, both PSA-CaCl(2) and PSA-GMA beads were incubated with Bacillus subtilis and Yersinia entercolitica as model contaminating microorganism. After 72 h, a release between 10 μM and 57 μM Alizarin was detected. For protection of the hydrogels, an enzymatically modified PET membrane was covalently attached onto the surface. This lead to a slower release and improve long term storage stability based on less than 1% release of dye after 21 days. Additionally, this allowed simple detection by visual inspection of the device due to a colour change of the white membrane to orange upon enzyme triggered release of the dye.

The recent withdrawal from the market of nadolol (Corgard; Bristol-Myers Squibb, Sermoneta, Italy) and quinidine polygalacturonate (Ritmocor; Malesci, Bagno A Ripoli, Italy) has been causing clinical problems to many cardiologists and patients, frequently leading to discontinuance of an effective and well-tolerated pharmacological treatment. Nadolol is useful in the treatment of severe and refractory arrhythmias, particularly in some genetically determined ion-channel diseases, such as long-QT syndrome and catecholaminergic polymorphic ventricular tachycardia.Quinidine is still used in refractory atrial fibrillation recurrences. Recent studies have demonstrated the clinical efficacy of quinidine in the treatment of rare genetically determined ion-channel diseases at high risk of sudden death, such as Brugada syndrome and short-QT syndrome.We hope that scientific societies can influence healthcare and pharmaceutical institutions, in order to restore the availability of two cardiovascular drugs that are extremely important in the care of arrhythmic patients.