Suppression of postoperative intimal hyperplasia of vein grafts with edaravone in rat models - a scanning electron microscope study

PURPOSE

Postoperative intimal hyperplasia, the most common cause of vein graft occlusion, is initiated by endothelial injury. In the present study, the mechanism by which the free radical scavenger edaravone (Radicut, Mitsubishi Tanabe Pharma Co, Japan) protects against endothelial injury in postoperative intimal hyperplasia was investigated.

METHODS

In 18 male Lewis rats, a right epigastric vein graft was interposed into the common femoral artery. Nine rats received a pre-operative intraperitoneal administration of edaravone (3.0 mg/kg, edaravone group) and the other nine rats received an equal volume of saline (saline group). After 1 h, five vein grafts from each group were treated with Verhoeff-van Gieson elastica stain and subjected to a histological examination. The other four vein grafts from each group were examined with an S-800 Hitachi scanning electron microscope (SEM) (Hitachi High-Technologies Co, Japan) at ×1000 magnification, as were three unoperated right epigastric veins (unoperated vein group). The endothelial areas of the vein grafts were measured using computerized planimetry of the SEM images (ImageJ version 1.37, National Institutes of Health, USA). The mean endothelial areas (%) were compared between the two groups.

RESULTS

Verhoeff-van Gieson elastica stain revealed no significant differences between the two groups. SEM showed that endothelial cells in the unoperated epigastric vein had a cobblestone-like appearance. In the saline group, the endothelial cells were comb-shaped and had adherent monocytes. In the edaravone group, however, the cobblestone-like appearance of endothelial cells was well preserved, with little monocyte adhesion. Moreover, the mean (± standard error of the mean) endothelial area was significantly higher in vein grafts from the edaravone group than in those from the saline group (74±1.8% versus 56±4.3%, P<0.05), and was similar to those in the unoperated epigastric veins (72±1.9%).

CONCLUSION

These findings show that endothelial injury is present soon after placement of the interposition graft. The authors believe that edaravone suppresses postoperative intimal hyperplasia by alleviating endothelial injury.     

Mizoribine therapy for patients with lupus nephritis: the association between peak mizoribine concentration and clinical efficacy

The clinical efficacy of mizoribine (MZR; 4-carbamoyl-1-b-d-ribofuranosylimidazolium) in patients with lupus nephritis was investigated. Thirteen Japanese patients with biopsy-proved lupus nephritis were enrolled in this study. A change in global assessments score, total protein (TP) of serum, serum creatinine, creatinine clearance (Ccr), proteinuria, titers of serum anti-ds DNA antibody, C3, C4, and hemolytic complement activity (CH50) were examined. Following MZR treatment, the level of urinary protein decreased (P < 0.05), whereas the level of Ccr increased (P < 0.05). Moreover, the level of TP significantly increased from 5.5 g/dl to 6.3 g/dl (P < 0.01) and the level of C3 increased significantly (P < 0.01). However, there was no change in the levels of both C4 and CH50. The titer of anti-ds DNA antibody significantly decreased (P < 0.05). The dosage of prednisolone could be tapered from 24.8 mg to 14.9 mg daily during the period. The clinical effects associated with MZR concentration in the blood revealed that there was a significant correlation between the peak MZR blood concentration of more than 0.66 μg/ml and clinical improvement (P = 0.021). Our results suggest that an optimal MZR blood concentration was important for the treatment of lupus nephritis. The first two authors contributed equally to this work.     

Prospective study of low-dose cyclosporine A in patients with refractory lupus nephritis

We evaluated the efficacy and safety of low-dose cyclosporine A (CsA) in patients with refractory lupus nephritis. Nine patients with systemic lupus erythematosus who had lupus nephritis resistant to previous treatment with glucocorticoids and immunosuppressants other than CsA were enrolled in a prospective, open-label study. All patients initially received 2.5 mg/kg per day of CsA; the dosage was adjusted to reach a blood trough level of 80–150 ng/ml. The urinary protein concentration decreased significantly 2 weeks after the initiation of treatment. After 30 weeks of CsA treatment, the mean urinary protein concentration was more than 50% lower than the baseline value, and urinary casts had decreased significantly. There were no significant changes in the levels of serum creatinine, serum anti-double-stranded DNA antibodies, or CH50 during any part of the study. The dose of glucocorticoids was significantly tapered by approximately 50%, without any disease flare. Hypertension developed in one patient, but was controlled with antihypertensive agents. Our results suggest that low-dose CsA therapy is an effective and less toxic alternative to conventional cyclophosphamide therapy for the management of refractory lupus nephritis.     

A novel ROCK inhibitor, Y-39983, promotes regeneration of crushed axons of retinal ganglion cells into the optic nerve of adult cats

We investigated the effect of a novel ROCK inhibitor, Y-39983, on neurite regeneration in vitro and axonal regeneration in the crushed cat optic nerve in vivo. To determine the effective dose for neurite regeneration, retinal pieces were cultured with ROCK inhibitors, Y-39983 or Y-27632, a well-characterized ROCK inhibitor, and the number and length of TUJ-1-positive neurites were evaluated. The greatest number of neurites protruded at a dose of 3-10 microM Y-39983 and at a dose of 10-100 microM Y-27632, respectively. The neurite number at maximum effect of Y-39983 was greater than that of Y-27632. No significant difference was observed between values of neurite length with the inhibitors. Based on this finding, we examined the effect of Y-39983 on axonal regeneration in the crushed optic nerve in vivo. Immediately after crushing the left optic nerve, Y-39983 was injected into the vitreous and the crushed site. An injection of 10 microM Y-39983 induced the crushed axons to regenerate and pass over the crush site. In contrast, very few axons passed beyond the crush site in the optic nerve with phosphate-buffered saline injection. The second injection of 10 microM Y-39983 on day 7 doubled the number of regenerated axons, suggesting that new axons may have entered into the optic nerve after day 7 and that a continuous supply of the drug may make more axons to regenerate.     

School children's salt intake is correlated with salty taste preference assessed by their mothers

Salt intake in childhood is a risk factor for developing hypertension later in life. As health education for children to decrease salt intake, it is important for them to know the relationship between salty taste preference and salt intake. The objective of this study was to investigate the relationship between children's salty taste preference and their salt intake. We employed a cross-sectional study design, and the subjects were 199 elementary school children (5th or 6th grade) and their mothers. The amount of salt intake was estimated by the amount of urinary sodium excretion. Children's salty taste preference was assessed 1) by asking children about their own salty taste preference as well as measuring their threshold level of salty taste, and 2) by their mothers' observation of their salt intake behavior using a questionnaire. The salt intake and salt taste threshold of children who liked a salty taste were similar to those in children who disliked it. No association was found between the threshold level of salty taste and sodium intake. Regarding the relationship between children's salt intake and their salt intake behavior score, assessed by their mothers using a questionnaire, the high score group had a higher estimated salt intake than the low score group. In conclusion, children's salt intake may be accurately assessed by their mother's observation rather than children's own salty taste preference. This study suggests the importance of a mother's role in salt restriction education for children.     

Serum cystatin C measured by a sol particle homogeneous immunoassay can accurately detect early impairment of renal function

BACKGROUND: A sol particle homogeneous immunoassay (SPIA) is a method to measure the serum cystatin C (cysC) level as a marker of the glomerular filtration rate (GFR). Recently, formulas to convert measured cysC to GFR have been developed. METHODS: A total of 154 patients (46 +/- 18 years old) who had undergone renal biopsy, sodium thiosulfate clearance (C thio) and 24-h creatinine clearance (24-hCcr) tests were subjects for the study. Their serum cysC levels were determined by SPIA. RESULTS: Multiple regression analysis revealed C (thio) and age as independent variables for serum creatinine concentration (Cr), while only C thio affected cysC. The equations using Cr or cysC showed significant correlation with C thio. Receiver-operating curve ROC analysis revealed that cysC and 24-hCcr shared comparable power to detect patients with GFR < 90 or 60 ml/min/1.73 m2 (AUC = 0.862 and 0.943 vs. AUC = 0.842 and 0.943, respectively), while Cr (AUC = 0.881) and MDRD2 (AUC = 0.888) showed slightly inferior ability to detect 60 ml/min/1.73 m2 than other parameters in the female population. The cut-off point of cysC and Cr obtained from the ROC analysis demonstrated strong power to detect patients with C thio < 90 ml/min/1.73 m2 or C thio < 60 ml/min/1.73 m2. According to CKD stages, the mean values of each equation were significantly different, like that demonstrated by 24-hCcr. CONCLUSION: SPIA could determine cysC levels that detected early renal impairment. The accuracy of cysC to detect early renal impairment may be superior to that of Cr in females, while it would be comparable to that of CG or MDRD when they are corrected by sex and age. Both cysC itself and cysC equations are effective to monitor the progress of renal impairment. The future standardization of cysC measurements and development of novel equation of cysC would contribute to the further improvement of GFR estimation in clinical practice.     

The subjective incremental cost of informed consent and documentation in hospital care: a multicentre questionnaire survey in Japan

Objective  To reveal the amount of time and financial cost required to obtain informed consent and to preserve documentation.
Methods  The questionnaire was delivered to all staff in six acute care public hospitals in Japan. We examined health care staff perceptions of the time they spent obtaining informed consent and documenting information. All data were collected in 2006 and estimates in the past week in 2006 were compared to estimates of time spent in a week in 1999. We also calculated the economic costs of incremental amounts of time spent in these procedures.
Results  In 2006, health care staff took about 3.89 hours [95% Confidence Interval (CI) 3.71–4.07] per week to obtain informed consent and 6.64 hours (95% CI 6.40–6.88) per week to write documentation on average. Between 1999 and 2006, the average amount of time for conducting informed consent was increased to 0.67 ( P  < 0.001) hours per person-week, and the average amount of time for documentation was increased to 0.70 ( P  < 0.001) hours per person-week. The annual economic cost of activities for informed consent and documentation in a 100-bed hospital increased from 117 755 to 449 402 US dollars.
Conclusions  We found a considerable increase in time spent on informed consent and documentation, and associated cost over a 7-year time period. Although greater attention to the informed consent process should be paid to ensure the notions of patient autonomy and self-determination, the increased resources devoted to these practices must be considered in light of current cost containment policies.