Involvement of iron-evoked oxidative stress in smoking-related endothelial dysfunction in healthy young men.

BACKGROUND: Oxidative stress and smoking contribute to endothelial dysfunction. Iron might also play a role in oxidative stress generation and endothelial dysfunction. However, the involvement of iron in smoking-induced endothelial dysfunction in healthy smokers remains unclear. Therefore, we examined here whether (1) intravenous iron infusion impaired endothelial function evaluated by flow-mediated vasodilatation (FMD) in non-smokers, and (2) deferoxamine, a potent iron chelator, ameliorated endothelial dysfunction in healthy smokers. METHODS: Eight healthy young male non-smokers (23 ± 4 years old) received intravenous injection of saccharated ferric oxide (0.7 mg/kg body weight), while 10 age-matched healthy male smokers received deferoxamine mesylate (8.3 mg/kg body weight). At baseline, 5 and 20 minutes after treatment with iron or deferoxamine, biochemical variables were measured, including serum iron and marondialdehyde (MDA), a marker of lipid oxidation, and endothelial function was simultaneously evaluated by FMD. RESULTS: Compared with non-smokers, FMD was significantly lower in smokers. Iron and MDA levels were significantly increased, whereas FMD was impaired by iron infusion in non-smokers. Conversely, deferoxamine treatment significantly decreased iron and MDA levels and restored the decreased FMD in smokers. Baseline serum iron and MDA levels in all 18 subjects (non-smokers and smokers) were correlated with each other. There was a significant inverse correlation between the changes in MDA values and FMD from baseline in 18 men. Endothelium-independent vasodilation by glyceryl trinitrate was unaltered by either treatment. CONCLUSIONS: Our present study suggests that iron-evoked oxidative stress might play a role in endothelial dysfunction in healthy smokers.

In vivo identification of sentinel lymph nodes using MRI and size-controlled and monodispersed magnetite nanoparticles.

PURPOSE: To develop a sentinel lymph node (SN) identification method using accurately synthesized magnetic nanoparticles (MNPs), as an enhanced specific SN tracer in combination with magnetic resonance imaging (MRI) in intact rodent and SN metastasis models. MATERIALS AND METHODS: Three sizes of MNPs were originally synthesized. We developed an experimental rat SN model, with brachial lymph nodes (Br) as the SN and the axillary lymph node (Ax) as the second lymph node, and injection of MNPs via the front paw. SN detectability was evaluated in vivo using T1 -weighted MR images after injection of the synthesized MNPs, and the amount of iron in the Br and in the Ax was assessed using inductively coupled plasma optical emission spectrometry. RESULTS: The highest ratios of the amount of iron in the Br versus the Ax were 3.1 and 3.3, using 20-nm MNPs after 2- and 24-hour injections. The appropriate dose and particle diameter for MRI detection was optimized, and the SN was optimally distinguished in the normal and metastatic rat models using MRI after a 0.4 mg/kg 20-nm MNP injection. CONCLUSION: We developed and optimized a useful SN identification method using MRI in rodent models.

Risk factors for postoperative recurrence in patients with pathologically T1 colorectal cancer.

BACKGROUND: The evolution of diagnostic procedures has resulted in an increase in early detection of pathologically T1 (pT1) colorectal cancer (CRC). However, the risk factors affecting long-term outcomes of patients with pT1 CRCs have been unclear. The aim of the present study was to identify risk factors for postoperative recurrence and overall survival in patients with pT1 CRC. METHODS: Between January 1990 and January 2003, a total of 284 patients with pT1 CRC underwent radical surgery in the authors' institution. The impact of clinicopathological factors on postoperative recurrence and overall survival was estimated by univariate and multivariate analysis. RESULTS: The median follow-up period was 55 months (interquartile range: 47.1 months). Postoperative recurrence occurred in 8 (2.8%) patients. The overall 5-year and 10-year disease-free survival rates were 98.4 and 92.7%. Multivariate analysis showed the presence of lymphatic invasion only was an independent risk factor for postoperative recurrence in pT1 CRC patients (hazard ratio: 11.622; P = 0.003). The 5-year and 10-year disease-free survival rates of the patients in N-ly- group, the N-ly + group, and the N+ group were 99.5%/98.2% and 96.3%/75.2%, and 93.3%/93.3%, respectively. Additionally, 4 of the 8 recurrences were found more than 5 years after the operation. CONCLUSIONS: Lymphatic invasion was an independent risk factor for recurrence in pT1 CRC patients.

Mesangiolytic glomerulopathy after radiotherapy and chemotherapy of gastric lymphoma.

Mesangiolytic glomerulopathy is an uncommon complication of irradiation and chemotherapy of THP-COP [pirarubicin, cyclophosphamide (CPA), vincristin (VCR), predonisolone (PSL)] and CHOP (CPA, Doxorubicin, VCR, PSL). We report a case of 63-year-old man 7 months status post radiation, and 10 months post chemotherapy for gastric lymphoma. The patient showed proteinuria and mild renal insufficiency. Renal biopsy revealed marked mesangiolysis in the glomeruli without any immune depositions. After the administration of angiotensin II receptor blocker, the patient's renal function remained stable for over two years. Mesangiolysis was thought to be a characteristic glomerular lesion in this patient treated with both chemoagents and radiation.

[Case of traditional herbal medicine-induced aristolochic acid nephropathy developing to end-stage renal failure].

A 48-year-old male was referred to our university hospital for severe azotemia with muscle cramp. He had been taking Chinese herbs as a traditional medicine to reduce hyperuricemia for about 9 months. Urinalysis showed trace proteinuria and hematuria without any casts. Renal glucosuria was also observed. In addition to azotemia, hyperchloremic metabolic acidosis and severe anemia were revealed. Hemodialysis was conducted and his general condition improved. A renal biopsy specimen revealed severe interstitial fibrosis and tubular atrophy with cellular degeneration. No remarkable glomerular changes were observed except for wrinkling of the basement membrane in a few glomeruli. Aristolochic acid was detected in the Chinese herbs, leading to the diagnosis of aristolochic acid nephropathy (AAN). His renal dysfunction was considered to be irreversible and he underwent maintenance hemodialysis. In Japan, AAN or Chinese herbs nephropathy decreased after an outbreak from 1995 to 2000. The public should be warned again that Chinese herbs, which are not permitted by the Japanese government, may contain aristolochic acid.