Taxanes and platinum derivatives impair Schwann cells via distinct mechanisms

Impairment of peripheral neurons by anti-cancer agents, including taxanes and platinum derivatives, has been considered to be a major cause of chemotherapy-induced peripheral neuropathy (CIPN), however, the precise underlying mechanisms are not fully understood. Here, we examined the direct effects of anti-cancer agents on Schwann cells. Exposure of primary cultured rat Schwann cells to paclitaxel (0.01 μM), cisplatin (1 μM), or oxaliplatin (3 μM) for 48 h induced cytotoxicity and reduced myelin basic protein expression at concentrations lower than those required to induce neurotoxicity in cultured rat dorsal root ganglion (DRG) neurons. Similarly, these anti-cancer drugs disrupted myelin formation in Schwann cell/DRG neuron co-cultures without affecting nerve axons. Cisplatin and oxaliplatin, but not paclitaxel, caused mitochondrial dysfunction in cultured Schwann cells. By contrast, paclitaxel led to dedifferentiation of Schwann cells into an immature state, characterized by increased expression of p75 and galectin-3. Consistent with in vitro findings, repeated injection of paclitaxel increased expression of p75 and galectin-3 in Schwann cells within the mouse sciatic nerve. These results suggest that taxanes and platinum derivatives impair Schwan cells by inducing dedifferentiation and mitochondrial dysfunction, respectively, which may be important in the development of CIPN in conjunction with their direct impairment in peripheral neurons

White blood cell count and cardiovascular biomarkers of atherosclerosis.

OBJECTIVE: To investigate the association with white blood cells (WBC) and atherosclerotic parameters including cardio-ankle vascular index (CAVI) and carotid intima-media thickness (CIMT) in the general population. METHODS: We investigated the relationship between WBC count and metabolic syndrome components, CAVI and CIMT in 3738 Japanese study participants. RESULTS: WBC count weakly correlated with CAVI in men (beta = 0.61, p = 0.043), but not in women (beta = 0.35, p = 0.17). On the other hand, WBC did not correlate with CIMT in either men or women (p = 0.41 and p = 0.71, respectively). CONCLUSION: WBC count was associated with lipids, blood pressure and body mass index, although the correlations with CAVI and CIMT were weak or absent

Enhanced monocyte migratory activity in the pathogenesis of structural remodeling in atrial fibrillation.

Background and aimsPathophysiological roles of monocytes in atrial fibrillation (AF), particularly for the progression of structural remodeling of the left atrium (LA), remain elusive. This study examined the association between the characteristics of circulating and local monocytes and extent of structural remodeling in LA, gauged by LA size, in AF patients.MethodsFirst, 161 AF patients who were referred for catheter ablation were enrolled and divided into two groups according to the median of LA diameter (≤39 mm: normal LA group, >39 mm: enlarged LA group). As a control group, 22 patients underwent catheter ablation for paroxysmal supraventricular tachycardia (PSVT) without history of AF were analyzed. Blood samples were collected for flow cytometric analyses to evaluate monocyte subsets based on the levels of CD14 and CD16. Moreover, monocytes were isolated from blood to measure CC chemokine receptor 2 (CCR2) transcripts and protein levels, and migratory activity toward monocyte chemoattractant protein 1 (MCP-1). Second, to characterize the local monocytes in the atrial wall in AF, the resected left atrial appendages (LAA) in AF patients underwent cardiac surgery were histologically evaluated (n = 20).ResultsThe proportions of monocyte subsets based on CD14 and CD16 expressions were not significantly different between the normal and enlarged LA group. Both transcripts and total protein levels of CCR2 in monocytes were higher in the enlarged LA group compared to those in the normal LA group. In the enlarged LA group, monocytes exhibited more enhanced migratory activity than the normal LA group. Moreover, we found a significantly higher number of CCR2-positive monocytes/macrophages in the LAA in the enlarged LA group.ConclusionEnhanced migratory activity in circulating and local monocytes may play a pivotal role in the pathogenesis of progression in atrial remodeling in AF patients

Start and initial results of the fukushima prefecture acute myocardial infarction registration survey

Acute myocardial infarction (AMI) remains one of the most serious heart diseases and elucidation of its pathogenesis and advances in treatment strategies have been desired. In 2009, to understand the status of AMI in Fukushima Prefecture for improving treatment outcomes, a new AMI registration survey system was conducted throughout the prefecture. A total of 1,556 cases were registered in the initial 2 years from 2009 to 2010. The hospital-based overall incidence of AMI in Fukushima Prefecture was 37.9 people per population of 100,000 per year. Mortality from AMI within 30 days of onset was 10.2%. We report herein the actual situation of AMI onset and treatment in Fukushima Prefecture based on the initial results of the survey

Acute myocardial infarction in Fukushima area of Japan

Although acute myocardial infarction (AMI) is the most serious coronary disease, the background of its onset and the mortality are not fully understood, especially in Japan. From June 1999 to May 2005, we mailed an annual questionnaire to eighteen hospitals in which emergency cardiac catheterization and percutaneous coronary intervention (PCI) were available in the Fukushima area of Japan. A total of 1,590 patients were included. The onset time of AMI had two peaks, i.e., from 9:00 AM to 10:00 AM and 9:00 PM to 10:00 PM. As for reperfusion therapy, four groups were analyzed, the non-reperfusion therapy group (Group N, n = 233), thrombolysis alone group (Group T, n = 80), PCI without thrombolysis group (Group P, n = 1106), and PCI with thrombolysis group (Group TP, n = 151). The in-hospital mortality rate was significantly reduced in Group P (8.4%) compared with that in Group N (33.0%, p < 0.01) and Group T (18.8%, p < 0.01). However, the in-hospital mortality in Group P did not differ from that in Group TP (9.9%). The in-hospital mortality was analyzed by the logistic regression analysis among age, arrival time after onset, peak creatine kinase (CK) values, coronary risk factors, reperfusion therapy, PCI, and thrombolysis. There were significant differences in age (P < 0.01), peak CK values (p < 0.01), hypertension (p < 0.05), and diabetes mellitus (p < 0.01). These results suggest that the onset of AMI may be partly related to human biorhythms, and that PCI would be effective in reducing the in-hospital mortality