Dopaminergic function and intertemporal choice

The discounting of delayed rewards, also known as temporal or delay discounting, is intrinsic to everyday decisions and can be impaired in pathological states such as addiction disorders. Preclinical and human studies suggest a role for dopaminergic function in temporal discounting but this relationship has not yet been verified using molecular imaging of the living human brain. Here, we evaluated dopaminergic function in temporal discounting using positron emission tomography (PET) with two different dopaminergic ligands assessing three populations in whom temporal discounting has been shown to be impaired. First, we show using [11C]raclopride PET that in pathological gamblers, greater temporal discounting correlates with decreased ventral striatal binding potential, convergent with translational findings of lower nucleus accumbens D2/D3 receptor density in high-impulsive rodents. Temporal discounting also correlates with lower ventral striatal dopamine release in response to high-reward magnitude suggesting that dopamine-mediated devaluation of larger delayed rewards may drive choice preferences. Second, we show using [18F]fluorodopa PET that in Parkinson''s disease, temporal discounting correlates with greater left caudate dopaminergic terminal function. Finally, in subjects with Parkinson''s disease and dopamine medication-induced behavioral addictions, temporal discounting is further correlated with greater dopaminergic terminal function in the anterior putamen. These findings provide insights into the relationship between striatal dopamine function and temporal discounting, and its potential role in pathological disorders and mechanisms underlying treatment interventions.     

Modulation of the expression of long-term cardiac memory by short-term cardiac memory in patients with Wolff-Parkinson-White syndrome after catheter ablation.

BACKGROUND: The interaction between long-and short-term cardiac memory (CM) is unknown. METHODS AND RESULTS: The T-wave areas and QTc intervals in each ECG lead were analyzed in 11 patients with manifest Wolff-Parkinson-White syndrome with posterior or septal accessory pathway (4 females; mean age: 47+/-12 years) in the following ECGs: (1) immediately after catheter ablation (post-ablation ECG); (2) immediately after 20 min of right ventricular outlet pacing (post-pacing ECG); and (3) 1 week after ablation (recovery ECG). Compared with the post-ablation ECGs, the T-wave areas of the recovery ECGs in leads II and aV(F) changed dramatically from negative to positive while that in lead III became less negative (p<0.01), and those in leads I, aV(L), and V(2-4) became less positive (p<0.05). Compared with the post-ablation ECGs, the T-wave areas of the post-pacing ECGs in leads III and aV(F) became less negative (p<0.01), and those in leads I, aV(L), and V(2-4) became less positive (p<0.05). The QTc interval in the post-ablation ECG was significantly longer than in either the post-pacing or recovery ECGs (p<0.05). CONCLUSIONS: Mechanisms involved in the expression of long-term CM could be affected by short-term CM.     

Treatment of aberrant facial nerve regeneration with botulinum toxin A

purpose To assess the effect and efficacy of botulinum toxin type A (BTX-A) at reducing and maintaining eyelid synkinesia in aberrant facial nerve regeneration, while concurrently observing for the presence of side effects to differing treatment doses. methods A prospective interventional study of five patients with eyelid synkinesia resulting from aberrant regeneration of the facial nerve. Patients were treated with injections of either 120, 80 or 40 units of BTX-A (Dysport) into the orbicularis oculi. Objective and subjective reduction in synkinesia, maintenance of response and presence of side effects were recorded. results All five patients had improvement of the synkinesia with BTX-A treatment. Lower doses were found to be as effective as higher doses. Mean duration of abolished synkinesia was three months. Two patients developed a ptosis which resolved spontaneously. None of the patients treated with the lowest dose of 40 units developed a ptosis. conclusion Low-dose BTX-A has a lower incidence of ptosis and is effective in the treatment of aberrant facial nerve regeneration.     

Overexpression of 2′,3′-Cyclic Nucleotide 3′-Phosphodiesterase in Transgenic Mice Alters Oligodendrocyte Development and Produces Aberrant Myelination

The function of the intracellular protein 2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNP) of oligodendrocytes (ODC) is unknown. We have now generated several homozygous transgenic mouse lines in which the human CNP gene is overexpressed up to sixfold, revealing new insights into early stages of myelinogenesis. Although no behavioral phenotype is immediately apparent, abnormalities of ODC and their myelin sheaths are striking. These are manifested as redundant myelin membrane and intramyelenic vacuoles, as well as lack of myelin compaction concordant with failure of the cytoplasmic leaflets of compact myelin to fuse. Further, ODC that overexpress CNP appear to mature earlier in development, resulting in earlier maximum gene expression for myelin basic proteins and proteolipid protein. These results indicate that CNP is an early expressed regulator of cellular events that culminate in CNS myelination.     

Effect of withdrawal of statin on C-reactive protein

BACKGROUND: C-reactive protein is considered a risk factor for coronary artery disease. In addition to its lipid-lowering properties, statin decreases the level of C-reactive protein. Abrupt cessation of statin therapy during treatment could increase the incidence of cardiac events in patients with atherosclerotic heart disease. The changes of C-reactive protein after withdrawal of statin therapy are still unknown. METHODS: Twenty patients with hyperlipidemia received statin (atorvastatin, 10 mg/day) therapy for 3 months. The levels of lipid profiles and C-reactive protein were assessed before receiving the statin therapy, immediately after 3 months of therapy, and on the 3 consecutive days after withdrawal of statin treatment. RESULTS: After 3 months of statin therapy, the total cholesterol, low-density lipoprotein cholesterol (LDL-chol), and C-reactive protein were significantly reduced (264.94 +/- 16.23 vs. 183.44 +/- 16.34 mg/dl, 183.17 +/- 34.56 vs. 122.00 +/- 17.66 mg/dl, and 2,309.00 +/- 437.85 vs. 1,257.95 +/- 207.99 ng/ml, respectively). The level of C-reactive protein increased on the second day after withdrawal of statin therapy (2,590.14 +/- 1,045.05 vs. 1,257.95 +/- 207.99 ng/ml); however, the total cholesterol and LDL-chol did not increase during the 3-day period after withdrawal of statin therapy. CONCLUSIONS: The increase in the level of C-reactive protein after withdrawal of statin therapy may be a contributing factor to the increased incidence of cardiac events in patients who have abruptly stopped statin therapy.     

Effect of electrophysiologic character of ventricular premature beat on heart rate turbulence

Heart rate turbulence (HRT) has been described as a predictor of high-risk patients with cardiac diseases. The purpose of this study is to determine how the degree of prematurity of a ventricular premature beat (VPB%) and retrograde ventriculoatrial (VA) conduction of VPBs affect HRT. We studied 30 patients without organic heart disease. We calculated turbulent slope (TS) and turbulent onset (TO) from VPBs induced by programmed stimulation from the right ventricular apex. TS was inversely and TO was positively correlated to VPB%. Without retrograde VA conduction of VPBs, TS was inversely and TO was positively correlated to VPB%. In VPBs with retrograde VA conduction, there were no significant correlations between TO and TS with VPB%. In conclusion, TS and TO calculated from VPBs with different degrees of prematurity varied widely. Both VPB% and characteristics of retrograde VA conduction may affect HRT.