oxadiazoles and Cardiomyopathies

Neuromuscular cardiopulmonary medicine is entering a new and exciting phase, with studies that assess the respiratory effect of emerging genetic and molecular therapies. In this year's neuromuscular Year in Review, we focus on Duchenne muscular dystrophy (DMD), reviewing studies that evaluate the respiratory effect of eteplirsen, the cardiopulmonary effects of ataluren, and a study comparing the use of spironolactone with eplerenone for the treatment of DMD-related cardiomyopathy.

Topics: Cardiomyopathies; Humans; Morpholinos; Muscular Dystrophy, Duchenne; Oxadiazoles; Spironolactone

Ten neonates with coxsackie B viral infection presented over a 3-month period. Clinical features included meningoencephalitis, thrombocytopenia, disseminated intravascular coagulopathy, cardiomyopathy, and hepatitis. Eight infants had multiorgan disease, four with severe myocardial dysfunction, of whom two died. All of the infants with severe disease developed symptoms within 7 days of age. In infants presenting within 10 days of birth, in all cases there were symptoms compatible with maternal infection prior to delivery. Severity was associated with perinatal transmission. Enteroviral polymerase chain reaction of CSF, urine, stool or throat swab was positive in nine of the ten babies. Seven of the infants were treated with a 7-day course of the new anti-picornaviral drug pleconaril (5 mg/kg 3 times daily).. These cases highlight the importance of not missing coxsackie B viral infection in the differential diagnosis of the septic neonate, especially as there is now a potential treatment.

Topics: Antiviral Agents; Cardiomyopathies; Coxsackievirus Infections; Disseminated Intravascular Coagulation; Enterovirus B, Human; Hepatitis; Humans; Infant; Infant, Newborn; Infant, Premature; Infectious Disease Transmission, Vertical; Meningoencephalitis; Oxadiazoles; Oxazoles; Perinatal Care; Polymerase Chain Reaction; Thrombocytopenia

An increase in the number of voltage dependent calcium channels has been implicated in the overload of calcium found in cardiac tissue of the cardiomyopathic hamster. We examined the binding of [3H]-(+)PN200110 to dihydropyridine receptors in cardiac muscle membranes from TO cardiomyopathic hamsters. When compared to random bred controls, there were no differences in either the Bmax or the KD for [3H]-(+)PN200110 binding using homogenates from 35 to 41-day-old TO cardiomyopathic hearts. In 8 to 9-month-old myopathic animals there were only small decreases in Bmax with no change in KD. We suggest that the calcium overload observed in cardiomyopathic hamster heart may not be due to an increased density of calcium channels as estimated by high affinity dihydropyridine receptor binding sites.

Topics: Animals; Calcium Channel Blockers; Calcium Channels; Cardiomyopathies; Cricetinae; Isradipine; Male; Myocardium; Oxadiazoles; Receptors, Nicotinic

The high affinity 1,4-dihydropyridine receptors of the cardiac membrane calcium channel from Syrian Cardiomyopathic hamsters were studied using [3H] PN200-110 and [3H]azidopine as ligands. [3H]Azidopine was photoincorporated covalently into bands of 180, 100, 79, 45 and 31 kDa, as determined by SDS/polyacrylamide gel electrophoresis. Photolabeling of the 180 kDa band is protected by 2 microM [1H]PN200-110 whereas the lower Mr bands are not. Thus, only the 180 kDa band is the calcium channel linked 1,4 dihydropyridine receptor. The photoincorporation into this 180 kDa band is doubled with samples of myopathic hamsters vs. control hamsters. It is suggested that the increase in calcium channel receptors may be involved in the pathogenesis of this cardiomyopathy.

Topics: Affinity Labels; Animals; Azides; Calcium; Calcium Channel Blockers; Calcium Channels; Cardiomyopathies; Cricetinae; Dihydropyridines; In Vitro Techniques; Ion Channels; Isradipine; Membrane Proteins; Molecular Weight; Myocardium; Oxadiazoles; Receptors, Nicotinic; Sarcolemma