Effects of safety warnings and risk management plan for Thiazolidinediones in Taiwan.

PURPOSE: To evaluate changes in thiazolidinedione use and quality of prescription following safety warnings for thiazolidinediones and cardiac risk in 2007, Risk Management Plan (RMP) policy for rosiglitazone in 2010, and warning for pioglitazone and bladder cancer risk in 2010 in Taiwan. METHODS: We obtained 2003-2011 claims data from Taiwan's National Health Insurance Research Database. Using an interrupted time series design and segmented regression, we estimated changes in monthly prescribing rates for thiazolidinediones among all and prevalent diabetes patients with and without cardiovascular disease history (CV history). We also compared time to prescription of thiazolidinediones among new diabetes patients with CV history before and after each regulatory action using survival analysis. RESULTS: Among prevalent patients with and without CV history, the prescribing rates of rosiglitazone decreased 36.88% and 28.92% after safety warnings in 2007 respectively. Pioglitazone prescriptions increased 13% among patients with CV history, but no changes were detected among patients without CV history. After rosiglitazone's RMP policy in 2010, large reductions in prescriptions were observed in patients with CV history (-101.67%) and those without CV history (-88.04%). Among new diabetes patients with CV history, cardiac safety warnings in 2007 significantly delayed the prescription of rosiglitazone, but no significant change was found for pioglitazone. CONCLUSIONS: The Taiwan FDA regulatory actions for thiazolidinediones communicated possible risks of cardiac events and bladder cancer. Different safety regulatory actions had differential impacts on the use of rosiglitazone and pioglitazone and the quality use of these drugs among the high-risk patients.

Functional connectivity changes during consolidation of inhibitory avoidance memory in rats: a manganese-enhanced MRI study.

Consolidation of memory involves transfer of encoded information into a durable neural representation, but how this is transacted in the nervous system remains elusive. It has been proposed that memory consolidation is subserved by formation of a cell assembly due to coincidence of pre- and post-synaptic activity therein after learning. To capture such off-line changes, manganese-enhanced magnetic resonance imaging (MEMRI) was used to trace brain activity during the memory consolidation period. Male Wistar rats were trained on the one-trial inhibitory avoidance task and received intraventricular infusion of manganese ion shortly after training. The MEMRI taken 1 day later showed that brain areas including the prelimbic, insular and anterior pirifrom cortices of the learning group had significantly lower memory-related MEMRI signal than those of the control group. The functional network was revealed by correlating the MEMRI signals among regions followed by graph theoretical analysis. Learning sculpted the non-discriminative connectivity among many brain regions in the controls into a network in the trained rats with selected connectivity among regions implicated in inhibitory avoidance learning. The network could be organized into three clusters presumably subserving different functions. The results suggest that the brain prunes excessive functional connectivity in a cell assembly to consolidate new memory.

Ceftriaxone prevents the neurodegeneration and decreased neurogenesis seen in a Parkinson's disease rat model: An immunohistochemical and MRI study.

Manganese-enhanced magnetic resonance imaging (MEMRI) is a widely used technique for detecting neuronal activity in the brain of a living animal. Ceftriaxone (CEF) has been shown to have neuroprotective effects in neurodegenerative diseases. The present study was aimed at clarifying whether, in an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) rat model, the known CEF-induced neuronal protection was accompanied by neurogenesis and decreased loss of neuronal activity. After MPTP lesioning (day 0), the rats were treated with CEF (100mg/kg/day, i.p.) or saline for 15 days. They were then injected with MnCl2 (40mg/kg, i.p.) on day 13 and underwent a brain MRI scan on day 14, then the brain was taken for histological evaluation on day 15. The results showed that MPTP lesioning resulted in decreased neuronal activity and density in the nigrostriatal dopaminergic (DAergic) system and the hippocampal CA1, CA3, and dentate gyrus (DG) areas and reduced neurogenesis in the DG, but in hyperactivity in the subthalamic nucleus (STN). These neuronal changes were prevented by CEF treatment. Positive correlations between MEMRI R1 values and neuronal density in the hippocampus were evidenced. Neuronal densities in the hippocampus and SNc were positively correlated. In addition, the R1 value of the STN showed a positive correlation with its neuronal activity but showed a negative correlation with the density of DAergic neurons in the SNc. Therefore, MEMRI R1 value may serve as a good indicator for PD severity and the effect of treatment. To our knowledge, this is the first study showing that CEF prevents loss of neuronal activity and neurogenesis in the brain of PD rats. CEF may therefore have clinical potential in the treatment of PD.