Cryothermal Catheter Ablation of Atrioventricular Nodal Reentrant Tachycardia in a Pediatric Patient after Atrioventricular Canal Repair

Anatomic displacement of the atrioventricular node and associated conduction tissue in atrioventricular septal defects has been previously described. In spite of the increasing use of cryothermal catheter ablation in the pediatric population, there remains very little literature regarding its use in congenital heart disease. We describe successful cryothermal modification of the slow atrioventricular nodal pathway in a 12-year-old patient with a previously repaired partial atrioventricular septal defect and inducible atrioventricular nodal reentrant tachycardia. The use of a steerable catheter to locate the displaced His signal combined with the use of cryothermal energy allowed for the safe and effective treatment of this patient's tachycardia.     

Dopaminergic neurons are preferentially sensitive to long-term rotenone toxicity in primary cell culture.

Parkinson's disease (PD) is a chronic neurodegenerative disorder characterized by the death of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the subsequent decrease of dopamine levels in the striatum. Epidemiological studies indicate environmental pollutants as a causative factor of sporadic PD. Experimental cell culture models have the inherent problem to mimic long-lasting neurodegeneration and to tackle its time-concentration relationship. The present study was designed to investigate the sensitivity of primary dopaminergic neurons to long-term rotenone exposure relevant to PD. Primary cultures prepared from embryonic mouse mesencephala were treated with nanomolar concentrations of rotenone (1, 3, 5, 10nM) on the 6th day in vitro (DIV) for 2, 4 and 6 days. The number of tyrosine hydroxylase immunoreactive (TH(+)) neurons and total hematoxylin-stained nuclei were counted. Astrocyte density was qualitatively evaluated by anti-glial fibrillary acidic protein (anti-GFAP) immunocytochemistry. It was found that dopaminergic neurons were highly sensitive to long-term rotenone treatment. Rotenone in a concentration- and time-dependent manner decreased the number of TH(+) neurons and led to degenerative changes of their morphology. Counting of the total cell number revealed a significant deleterious effect on the overall culture after 6 days of rotenone exposure. However, our study demonstrates a higher sensitivity of dopaminergic neurons to long-term exposure to nanomolar concentrations of rotenone. Other cells in the culture including non-dopaminergic neurons and glia cells appeared less affected compared to dopaminergic neurons.     

Pergolide protects dopaminergic neurons in primary culture under stress conditions

Summary. Dopamine agonists are an important therapeutic strategy in the treatment of Parkinson's disease. They postpone the necessity for and reduce the required dose of L-3,4-dihydroxyphenylalanine (L-DOPA) medication thus protecting against the development of motor complications and potential oxidative stress due to L-DOPA metabolism. In primary cultures from mouse mesencephalon we show that pergolide, a preferential D₂ agonist enhanced the survival of healthy dopaminergic neurons at low concentrations of 0.001 μM. About 100 fold higher concentrations (0.1 μM) were necessary to partially reverse the toxic effects of 10 μM 1-methyl-4-phenylpyridinium (MPP⁺). Pergolide was equally effective in preventing the reduction of dopamine uptake induced by 200 μM L-DOPA. Furthermore, between 0.001–0.1 μM it also reduced lactate production thus promoting aerobic metabolism. The present findings suggest that pergolide protects dopaminergic neurons under conditions of elevated oxidative stress. Received February 4, 2002; accepted February 21, 2002     

Use of high-content analysis for compound screening and target selection

High-content analysis (HCA) has rapidly established itself as a core technology in drug discovery for secondary cell-based screening. When combined with our knowledge of genetics, HCA can provide a powerful tool for target validation, but excitingly, HCA may also enable the increased use of cellular assays in high-throughput screening for novel drug leads.     

Cognitive strategies in patients with unilateral temporal lobe excisions

The performance of patients with surgical excisions of either the left or right temporal lobe and a normal control group was compared on a hypothesis test. Subjects in both temporal lobectomy groups solved fewer problems than controls; and there was no difference in the performance of left and right lobectomy patients. However, analyses of cognitive patterns revealed specific strategies associated with subjects having undergone left temporal lobe excisions. These patients formulated fewer hypotheses than controls and tended to shift from a given hypothesis even when it was indicated to be correct. Conversely, right temporal lobectomy patients tended to retain a given hypothesis which was indicated to be incorrect. The same results were found with and without memory assistance, indicating that these cognitive strategies occur independent of overt memory deficits.     

Rational combinatorial design of pore-forming beta-sheet peptides

Exogenous polypeptides that self-assemble on biological membranes into pores are abundant and structurally diverse, functioning as transporters, toxins, ion channels, and antibiotics. A means for designing novel pore-forming sequences would unlock new opportunities for the development and engineering of protein function in membranes. Toward this goal, we designed a 9,604-member rational combinatorial peptide library based on the structural principles of known membrane-spanning beta-sheets. When the library was screened under stringent conditions for sequences with pore-forming activity, a single active motif was found, which is characterized by aromatic residues at the lipid-exposed interfacial positions and basic residues in the pore-lining portion of the sequence. Peptides with this motif assembled on bilayer membranes into beta-sheets and formed transient peptide/lipid pores of approximately 1-nm diameter. The mechanism of action is very similar to that of natural, pore-forming peptides. These methods provide a powerful means for selecting and engineering novel pore-forming sequences and will open prospects for designing peptide antibiotics, biosensors, and new membrane protein structures.