Iron-induced tissue damage and cancer: The role of reactive oxygen species-free radicals

Oxygen is poisonous, but we cannot live without It. The high oxidizing potential of oxygen molecules (dioxygen) Is a valuable source of energy for the organism and its reactivity is low; that is, spin forbidden. However, the dioxygen itself is a 'free radical' and, especially in the presence of transition metals, K is a major promoter of radical reactions in the cell. Humans survive only by virtue of their elaborate defense mechanisms against oxygen toxicity.
Iron is the most abundant transition metal in the human body- Because iron shows wide variation in redox potential with different co-ordination ligands, it may be used as a redox intermediate in many biological mechanisms. However, it is precisely this redox activeness that makes iron a key participant in free radical production.
The current research on the relationship between iron and cancer is briefly reviewed. Research results are reported here which indicate that iron, when bound to certain ligands, can cause free-radical mediated tissue damage and become carcinogenic. The present study also suggests that iron may also have a significant role in spontaneous human cancer.     

Advanced Neuroblastoma and Disseminated Intravascular Coagulation: Report of Six Cases

We have experienced 30 patients with neuroblastoma since 1975.Disseminated intravascular coagulation (DIC) developed in sixof these patients. They were all in stage IV, namely disseminatedneuroblastoma. These six cases with DIC proved that some advancedneuroblastomas have the potential to cause coagulopathy in theprocess of the disease. The plasma concentration of heparin was measured in some patientswho were treated with heparin. The data revealed that the conventionallyused intravenous heparin dose is not appropriate in the caseof DIC. Effective treatment requires monitoring of the plasmaconcentration of heparin.     

A case of ureteral reflux identified by ultrasound

Reflux nephropathy is known to be a major cause of renal failure in children. Vesico-ureteral reflux is usually diagnosed by voiding cysto-urethrography (VCG). However, it has been observed that conventional VCG is not always reliable for the diagnosis of ureteral reflux. In the case of a 5 year old girl with recurrent febrile urinary tract infection, VCG showed no ureteral reflux. Urodynamic study revealed a large bladder capacity and significant residual urine. Renal scintigram delineated a right renal scar. Simple ultrasound examination with videotape recording during voiding definitely demonstrated the presence of significant ureteral reflux when she voided, that is, there was marked dilatation of the right distal ureter and ballooning of the right renal pelvis on voiding, and quick refilling of the bladder concomitantly with the disappearance of the pelvic ballooning. Therefore, an ultrasound during voiding may be useful for diagnosing ureteral reflux in patients where a VCG does not reveal reflux.     

Lipoprotein (a) and apolipoprotein A-1 and B in schoolchildren whose grandparents had coronary and cerebrovascular events: A preliminary study of 12–13 year old Japanese children

The aim of this study was to evaluate the relationship between the serum levels of lipoprotein (a) [Lp (a)] and apolipoproteins (apo A-1 and apo B) in schoolchildren with a history of coronary and cerebrovascular events in their grandparents. We measured serum concentrations of Lp (a) and apoliproteins immunochemically in 289 schoolchildren aged 12–13 years and questioned parents about coronary and cerebrovascular events in the children's grandparents. In boys and girls, mean ± s.d. levels of apo A-1, apo B and Lp (a) were 134 ± 20.3 and 136 ± 17.4 mg/dL, 61 ± 16 and 66 ± 15 mg/dL and 12.5 ± 15.3 and 12.5 ± 15.1 mg/dL, respectively. There were no significant sex differences in the levels of apo A-1, apo B, and Lp (a). The Lp (a) levels (mean ± s.d., 12.5 ± 15.2 mg/dL; median 7.5 mg/dL, n = 289) were not affected by other variables. The Lp (a) distribution was strongly positively skewed and 75% of schoolchildren had very low levels. In the total 289 schoolchildren, thirty-two grandparents who had had coronary vascular events (21 myocardial infarction, 11 angina pectoris) and twenty-three grandparents who had had cerebrovascular events were recorded. By the boxplot statistical analysis, no difference was found in Lp (a) levels in children whose grandparents had myocardial infarction compared with those whose grandparents had no such history, or compared with those whose grandparents had suffered cerebrovascular events. Analysis also showed that the values of log Lp (a) in children whose grandparents had myocardial infarction tended to be higher than the values in children whose grandparents had no such history (P = 0.09). No significant differences in the levels of apo A-1 and apo B and in the apo B/A-1 ratio could be seen between children grouped according to the presence or absence of coronary and cerebrovascular events in their grandparents. These results suggest that high levels of Lp (a) in schoolchildren aged 12–13 years may partly reflect the existence of coronary vascular disease in older family members. Lp (a) may account for the strongest index of family history to disease risk in comparison with other apolipoproteins. Further study is needed to clarify the appropriate mass measurement method for Lp (a) in schoolchildren.     

Mycophenolate mofetil therapy for children with intractable nephrotic syndrome

BACKGROUND: Cyclosporin A (CyA) can suppress relapses and reduce proteinuria in frequent-relapse nephrotic syndrome (FRNS) and steroid-resistant nephrotic syndrome (SRNS). However, some patients remain resistant to CyA therapy. The purpose of the present paper was to evaluate mycophenolate mofetil (MMF) treatment in pediatric patients with CyA-resistant intractable nephrotic syndrome. METHODS: MMF therapy was given to 11 patients with FRNS who had relapse despite CyA therapy, and one patient with SRNS who had been receiving combined therapy using steroid and CyA until immediately before the start of MMF. MMF was administered at a daily dose of 750-1000 mg/m(2) in two divided doses. RESULTS: Ten of the 11 patients with FRNS were able to maintain remission. Among them, seven patients remained relapse free for 1 year, and two patients had a decrease in the frequency of relapse after initiation of MMF therapy. One patient, however, had repeated cycles of remission and relapse, and was considered resistant to MMF therapy. The total prednisolone dose during the period from month 6 to month 12 after the start of MMF therapy was significantly lower than that during the 6 month period before the start of MMF therapy. The patient with SRNS, who had not achieved remission despite CyA administration, had complete remission on MMF. No serious adverse effects were seen in any of the present patients. CONCLUSION: MMF could be useful in CyA-treatment-refractory FRNS and CyA-resistant SRNS.     

Bronchoscopic practice in Japan: A survey by the Japan Society for Respiratory Endoscopy in 2010

Background and objective: To ensure the safety of bronchoscopic practice, the Japan Society for Respiratory Endoscopy conducted a national survey to investigate the current state of procedure for this technique. Methods: A questionnaire survey about procedures carried out during the whole of the year 2010 was mailed to 538 facilities accredited by the society. Results: Responses were obtained from 511 facilities (95.0%). Rigid bronchoscopes were used in only 18.5% of the facilities, while mobile/thin bronchoscopes were used in ≥50%, and fluoroscopy systems were used in 99.8%. Biopsies were performed after discontinuation of therapy in patients receiving antiplatelet drugs and anticoagulants in 96.7% and 97.4% of the facilities, respectively. Atropine was administered for premedication in 67.5% of the facilities, a decrease from previous surveys. Intravenous sedation was given in 36.1% of the facilities. In 21.9% of these, the procedure was conducted in the outpatient clinic for ≥70% of patients. A bronchoscope was orally inserted in ≥70% of patients in 95.7% of the facilities. Intravenous access was maintained during the examination in 92.5% of the facilities, oxygen saturation was monitored during examinations in 99.0%, oxygen was administered in 97.6% and resuscitation equipment was available in 96%. In 98.6% of the facilities, bronchoscopes were disinfected using an automatic washing machine, with glutaraldehyde used in 42.2%. Conclusions: Japan‐specific characteristics of bronchoscopic practice were identified. Whether procedures used in Japan meet international guidelines with respect to safety should be monitored continuously. In addition, a Japanese evidence‐based consensus is needed.     

五苓散考

五苓散是五味猪苓散的略称,其方义随<伤寒论>的变迁而不同.<全匮要略>呕吐篇中的三味猪苓散和<伤寒论>五味猪苓散(即五苓散)是起源不同的方剂;<宋版伤寒论>中五苓散和猪苓散虽是利尿剂,但见证脉浮,脉浮意味着"先用发汗法,次用吐法",是编集者避忌过激发汗法和吐法的结果,使五苓散(猪苓散)原来作为吐剂使用的事实变得模糊.实...     

Use of Protease Inhibitors to Improve Calcitonin Absorption from the Small and Large Intestine in Rats

The objective of this study was to examine the effects of protease inhibitors on the absorption of calcitonin from different regions of the intestine in rats. The absorption experiments were investigated by in-situ use of closed intestinal loops in rats and stability of calcitonin was examined in mucosal homogenates and intestinal fluids. The intestinal absorption of calcitonin was evaluated by measurement of its hypocalcaemic effect. No substantial hypocalcaemic response was observed when calcitonin was administered into the jejunum or colon. A slight hypocalcaemic effect was observed after administration of calcitonin into the ileum. Of the co-administered protease inhibitors, bacitracin (20 mM) strongly promoted calcitonin absorption from the jejunum, ileum and colon. A significant hypocalcaemic effect was also obtained after intestinal administration of calcitonin with soybean trypsin inhibitor (10mgmL^?1), camostat mesylate (20mM) or aprotinin (2mgmL^?1). In the stability experiment, bacitracin reduced the degradation of calcitonin in the different intestinal homogenates. Soybean trypsin inhibitor significantly reduced the degradation of calcitonin in the fluids of the small intestine. We also examined the different endopeptidases in gut luminal fluids and the different exopeptidases in gut mucosal homogenates of rats. The ranking order for the total endopeptidase activity of the intestinal fluids was jejunum > ileum > colon. That for total exopeptidase activity of the intestinal mucosa was jejunum > ileum > colon. These results suggest that endo- and exopeptidases might be responsible for the hydrolysis of calcitonin and that protease inhibitors might usefully improve absorption of calcitonin to the systemic circulation from the large intestine.