ABSTRACT
The efficacy of pharmacological disruption of fear memory reconsolidation depends on several factors, including memory strength and age. We built on previous observations that systemic treatment with the nootropic nefiracetam potentiates cued fear memory destabilization to facilitate mifepristone-induced reconsolidation impairment. Here, we applied nefiratecam and mifepristone to strongly conditioned, 1-wk-old contextual fear memories in male rats. Unexpectedly, the combined treatment did not result in impairment of contextual fear expression. However, mifepristone did reduce freezing to a novel context. These observations suggest that strong and established contextual fear memories do undergo destabilization without the need for pharmacological facilitation, and that impairments in strong context fear memory reconsolidation can manifest as a reduction in generalization.
Subject(s)
Fear/drug effects , Generalization, Psychological/drug effects , Memory/drug effects , Mifepristone/toxicity , Nootropic Agents/toxicity , Animals , Conditioning, Psychological/drug effects , Extinction, Psychological , Freezing Reaction, Cataleptic , Male , Pyrrolidinones/pharmacology , RatsABSTRACT
There are limited data on total dose infusion (TDI) using iron dextran in geriatric chronic kidney disease (CKD) patients with iron-deficiency anemia (IDA). Our goal was to evaluate the safety of TDI in this setting. We conducted a retrospective chart review spanning a 5 year period (2002-2007), including all patients with CKD and IDA who were treated with iron dextran TDI. Patient demographics were noted, and laboratory values for creatinine, hemoglobin and iron stores were recorded pre- and post-dose. TDI diluted in normal saline was administered intravenously over 4-6 hours after an initial test dose. One hundred fifty-three patients received a total of 250 doses of TDI (mean ± SD=971 ± 175 mg); age was 69 ± 12 years and creatinine 3.3 ± 1.9 mg/dL. All stages of CKD were represented (stage 4 commonest). Hemoglobin and iron stores improved post-TDI (P<0.001). None of the patients experienced an anaphylactic reaction or death. Adverse events (AEs) were noted in 8 out of 250 administered doses (3.2%). The most common AEs were itching, chills and back pain. One hundred and ten doses of high molecular weight (HMW) iron dextran produced 6 AEs (5.45%), whereas 140 doses of low molecular weight (LMW) iron dextran produced 2 AEs (1.43%), a non-significant trend (P=0.1433 by Fishers Exact Test). Iron dextran TDI is relatively safe and effective in correcting IDA in geriatric CKD patients. Fewer AEs were noted with the LMW compared to the HMW product. LMW iron dextran given as TDI can save both cost and time, helping to alleviate issues of non-compliance and patient scheduling.
Subject(s)
Anemia, Iron-Deficiency/drug therapy , Hematinics/administration & dosage , Iron-Dextran Complex/administration & dosage , Renal Insufficiency, Chronic/complications , Aged , Aged, 80 and over , Anemia, Iron-Deficiency/etiology , Humans , Infusions, Intravenous , Middle Aged , Retrospective StudiesABSTRACT
Purpose. We sought to investigate the effect of IV iron repletion on platelet (PLT) counts in CKD patients with iron deficiency anemia (IDA). Methods. We conducted a retrospective chart review, including all patients with CKD and IDA who were treated with iron dextran total dose infusion (TDI) between 2002 and 2007. Patient demographics were noted, and laboratory values for creatinine, hemoglobin (Hgb), iron stores and PLT were recorded pre- and post-dose. Results. 153 patients received a total of 251 doses of TDI (mean ± SD = 971 ± 175 mg); age 69 ± 12 years and Creatinine 3.3 ± 1.9 mg/dL. All CKD stages were represented (stage 4 commonest). Hgb and Fe stores improved post-TDI (P ⪠0.001). There was a very mild decrease in PLT (pre-TDI 255 versus post-TDI 244, P = 0.30). The mild reduction in PLT after TDI remained non-significant (P > 0.05) when data was stratified by molecular weight (MW) of iron dextran used (low versus high), as well as by dose administered (<1000 versus ≥1000 mg). Linear regression analysis between pre-dose PLT and Tsat and Fe showed R2 of 0.01 and 0.04, respectively. Conclusion. Correction of iron deficiency did not significantly lower PLT in CKD patients, regardless of MW or dose used. Correlation of PLT to severity of iron deficiency was very weak.
