The impact of 5-formyltetrahydrofolate on the anti-tumor activity of pralatrexate,as compared to methotrexate,in HeLa cells in vitro

Purpose

To investigate the impact of 5-formyltetrahydrofolate on the activities of pralatrexate, as compared to methotrexate (MTX), in vitro.

Methods

Cells were exposed to (6S)5-formyltetrahydrofolate (5-formylTHF) for 24 h, before or after a 6-h exposure to antifolates following which the cellular accumulation and activities of the drugs were evaluated in HeLa cells.

Results

A 24-h delay between a 6-h exposure to antifolates and a subsequent 24-h exposure to 4 μM 5-formylTHF sustained the full activities of both antifolates. A 72-h interval was required between a single exposure of up to 4 μM 5-formylTHF and subsequent exposure to drugs to sustain activities of the antifolates. When cells were incubated with 4 μM 5-formylTHF for 24 h weekly, for 4 weeks, there was no significant increase in the IC₅₀ for pralatrexate, but the MTX IC₅₀ increased 2.5-fold as compared to cells growing continuously in 25 nM 5-formylTHF. This cyclical exposure to 5-formylTHF increased the cell folate pool by 16 %, had no significant effect on the intracellular pralatrexate level, but decreased intracellular MTX by 15 %. An extracellular concentration of MTX 50-fold higher than that of pralatrexate was required to achieve an intracellular level, and growth inhibition, comparable to that of pralatrexate.

Conclusions

Cyclical exposures to 5-formylTHF at levels in excess of what is achieved in most clinical “rescue” regimens do not affect pralatrexate accumulation nor antitumor activity in HeLa cells, in contrast to MTX. An important element in preserving pralatrexate activity is achieving a sufficient interval between exposure to 5-formylTHF and the next dose of antifolate.     

术前肌电图和脑干听觉诱发电位与面肌痉挛微血管减压术后迟发性面瘫发生的关系(英文)

Background Delayed facial palsy ( DFP) after microvascular decompression ( MVD) in patients with hemifacial spasm ( HFS) is not uncommon,but the cause remains unknown. Objectives To assess whether intraoperative electromyography ( EMG) and brainstem auditory evoked potential ( BAEP) can predict DFP after MVD. Methods Between September 2009 and February 2011 we examined 86 patients,9 of whom ( 10. 4% ) developed DFP after MVD on the same side. All patients underwent MVD and were followed - up for a median period of 13 months ( range 6-22) . We retrospectively examined intraoperative facial EMG and BAEP findings using our MVD patients’ registry. We excluded secondary HFS and immediate postoperative facial palsy after MVD in this study. We assessed the prevalence and clinical characteristics of DFP and compared EMG and BAEP findings between DFP and non-DFP groups. Results: All pa- tients recovered completely,with a mean time to recovery of 37. 8 days ( range 22-57) . There were no significant differences between DFP and non - DFP patients in terms of the amplitude and latency of intraoperative EMG and BAEP. Conclusion The usefulness of intraoperative facial EMG and BAEP is limited and cannot predict DFP after MVD for HFS. We speculate that DFP after MVD is not associated with permanent nerve damage according to the EMG findings.     

男性乳腺发育症的超声表现和诊断评估

目的了解男性乳腺发育症的年龄特征和超声图像表现。方法回顾性分析我院近10年经病理证实和临床随访诊断的1618男性乳腺发育症患者的临床、超声和病理资料。结果 1618例患者年龄呈双峰分布,发病高峰为16～20岁,其次为36～40岁。其声像图表现可分为结节型(41.9%)、树根型(11.6%)和类女性乳腺型(46.5%);手术组83例腺体层厚度(12.2±4.3)mm,与非手术组1535例腺体层厚度(8.3±4.8)mm比较差异有统计学意义(P<0.05),超声诊断男性乳腺发育症的敏感性为92.0%,特异性为94.7%,准确性为93.3%。结论超声测量男性乳腺腺体厚度是临床治疗的客观依据,超声检查可作为首选。     

Use of amplitude-integrated electroencephalography (aEEG) and near infrared spectroscopy findings in neonates with asphyxia during selective head cooling

Background

Amplitude-integrated electroencephalogram (aEEG) at <6 h is the best single outcome predictor in term infants with perinatal asphyxia at normothermia. Hypothermia treatment has changed the cutoff values for outcome prediction by using time at onset of normal trace and SWC. Cerebral hemodynamics and oxygenation changes detected by near infrared spectroscopy (NIRS) during hypothermia treatment in aphyxiated neonates are not a well known issue.

Aim

The aim of this study was to investigate the correlations between brain monitoring (amplitude integrated EEG and NIRS) and outcome in asphyxiated full-term infants with moderate/severe hypoxic–ischemic encephalopathy before, during and after hypothermia treatment.

Method

Ten neonates were recruited for hypothermia treatment by using the cool cap entry criteria. aEEG and NIRS were applied in 10 and 8 patients, respectively with moderate and severe hypoxic–ischemic encephalopathy before, just after brain cooling and rewarming periods. Patterns and voltages of aEEG backgrounds sleep–wake cycles (SWC) and NIRS values (TOI% and FTOE) were recorded. During the follow up their outcomes were assessed by using the Bayley Scales of Infant Development II.

Conclusion

Hypothermia changes the predictive value of early aEEG. Normalization of a baby’s aEEG and the appearance of SWCs while being cooled occurs later. In our study one patient had normal aEEG background pattern at 80 and imminent SWC at 90 h after birth and still had normal Bayley scores at 24 months. Time to normal aEEG and SWC appearance should be carefully evaluated during the cooling period. NIRS values were different due to the clinical presentations of the patients.     

Plerixafor use in patients with previous mobilization failure: A multicenter experience

Plerixafor in conjunction with G-CSF (G-P) is an effective strategy for hematopoietic stem cell mobilization in patients with previously failed mobilization attempt. Here we report our results with G-P among patients with at least one mobilization failure with G-CSF alone (G) or G-CSF plus chemotherapy (G-C). The study included 20 consecutive patients with lymphoma and myeloma from five centers. In 14 (70%) patients, a minimum of 2×10(6)/kg CD34+ stem cells were collected and 16 out of 20 patients (80%) were able to proceed to ASCT. Our study indicates that plerixafor can safely rescue patients with a history of mobilization failure.     

The protective effect of amiodarone in lung tissue of cecal ligation and puncture-induced septic rats: a perspective from inflammatory cytokine release and oxidative stress

Sepsis is a serious medical condition that is characterized by a whole-body inflammatory state and the presence of a known or suspected infection. Amiodarone is a class III antiarrhythmic agent, a multichannel blocker (Ca++, Na+, and K+), and a noncompetitive α- and β-adrenergic blocker in cardiac cells. The present study aimed to determine whether amiodarone was protective against experimentally induced cecal ligation and puncture sepsis in rat lung tissue. The relationship between its probable protective effect and antioxidant/anticytokine action biochemically and histopathologically was also examined. Five groups of rats were used, each composed of 20 rats: (1) the sham-operated control group; (2) the CLP group; (3) the 25-mg/kg amiodarone-treated control healthy group; (4) the 50-mg/kg amiodarone-treated CLP group; and (5) the 50-mg/kg amiodarone-treated CLP group. A CLP polymicrobial sepsis model was applied to the rats. All groups were sacrificed 16 h later, and lung and blood samples were analyzed histopathologically and biochemically. Twenty-five and 50 mg/kg amiodarone decreased the level of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α in serum and 8-iso-prostaglandin F2α level in lung tissue. They increased the activities of superoxide dismutase and levels of total glutathione in lung tissues of rats. Histopathological scores and examinations were in accordance with the biochemical results. Histopathological analysis revealed significant differences in inflammation scores between the sepsis group and the other groups. The CLP?+?amiodarone 50 mg/kg group had the lowest inflammation score among CLP groups. Our results indicate that administration of amiodarone prevented oxidative stress and cytokine action and protected lung tissue during sepsis cascade.