On-road exposure to highway aerosols. 2. Exposures of aged, compromised rats

Ambient particulate pollution is associated with adverse health effects in epidemiological studies of the elderly with cardiopulmonary diseases. We hypothesize that ultrafine particles (UFP) contribute to these effects, especially when they are freshly generated and occur at high number concentrations. Studies to determine adverse effects have been performed using laboratory-generated surrogates, diluted exhaust from stationary engines, or concentrated ambient UFPs. Methodological difficulties exist with such experiments, and questions remain about how well these particles model those found in ambient air. Freshly generated UFPs are present at high concentrations on highways and vehicle passengers are directly exposed to them. We wished to expose rats to these UFPs to test their potential to cause effects. Since such exposures have not been done before, one objective of our study was to demonstrate the feasibility of an on-road exposure study. Secondly, we wished to determine if there are significant exposure-related effects in aged, compromised rats. Old rats (21-mo F-344) were exposed directly on highways to either the aerosol (<1 microm)/gas phase, gas phase only, or filtered air using an on-road exposure system. Some rats were pretreated with a low dose of inhaled endotoxin or with instilled influenza virus to induce lung inflammation. The exposures in compartmentalized whole-body chambers consisted of 6-h driving periods on I-90 between Rochester and Buffalo once or 3 days in a row. Endpoints related to lung inflammation, inflammatory cell activation, and acute-phase responses were measured after exposure. The on-road exposure system did not affect measured endpoints in filtered air-exposed rats, indicating that it was well tolerated by them. We observed the expected increases in response (inflammation, inflammatory cell activation) to the priming agents. We also found a significant particle-associated increase in plasma endothelin-2, suggesting alterations in vascular endothelial cell activation. In addition, we observed main effects of particles related to the acute-phase response and inflammatory-cell activation. Interactions between on-road particles and the priming agents were also found. These results suggest that exposures to on-road particle mixtures have effects on the pulmonary and cardiovascular system in compromised, old rats. Furthermore, they demonstrate that on-road exposures are feasible and could be performed in future studies with more continuous particle exposures.     

Tyrosinase-inhibitory furanocoumarin from Angelica dahurica

An extract of the roots of Angelica dahurica BENTH. et HOOK. (Umbelliferae) showed potential tyrosinase inhibition against mushroom tyrosinase. Employing a bioassay-linked HPLC method, followed by semipreparative HPLC, the active principle was isolated and characterized as 9-hydroxy-4-methoxypsoralen.     

The Seoul Metropolitan Preschool Vision Screening Programme: results from South Korea

AIM: To report on a new model of preschool vision screening that was performed in metropolitan Seoul and to investigate the distribution of various ocular disorders in this metropolitan preschool population. METHODS: Vision screening was conducted on 36 973 kindergarten children aged 3-5 years in a stepwise manner. The first step was home screening using a set of five picture cards and a questionnaire. The children who did not pass the first step (VA <0.5 in at least one eye or any abnormal responses on the questionnaire) were retested with regular vision charts at the regional public healthcare centres. After this retest, some children were referred to ophthalmologists. The referral criteria for visual acuity were <0.5 at 3 years and <0.63 at 4 or 5 years in at least one eye. RESULTS: Of those screened, 7116 (19.2%) children did not pass the home screening tests and 2058 (28.9%) out of the 7116 were referred. The results of the ophthalmological examination in eye clinics were only available for 894 children (43.4%) of those who were referred. The rest of the children did not visit ophthalmologists because they had been checked at an eye clinic, were currently under treatment, or for personal reasons. Refractive errors were found in 608 (1.6%) children. Astigmatism was associated in 78.2% of ametropes. Amblyopia was discovered in 149 (0.4%) children and refractive error was the major aetiology with a predominant rate (82.5%). Manifest strabismus was detected in 52 children. The positive predictive value of vision screening for any ophthalmological disorder was 0.77, and 0.49 for significant disorders requiring treatment. CONCLUSIONS: This preschool vision screening model was highly accessible to the children and their parents, easy to administer, and effective to detect a variety of ocular disorders. However, the participation rate of the referred children in the examinations by ophthalmologists was quite low. The performance and efficiency of this screening programme need to be optimised with further revision.     

Use of polyurethane with sustained release dexamethasone in delayed adjustable strabismus surgery

AIM: To determine the effect of polyurethane film with sustained release dexamethasone (SRD) in delayed adjustable strabismus surgery. METHODS: A prospective, masked observer, controlled study was performed in rabbits. Thirty four rabbit eyes were divided into three groups. After recession of the superior rectus muscle (SRM), polyurethane film with or without SRD, or balanced salt solution was applied beneath and over SRM in the polyurethane-dexamethasone group (group P-D), polyurethane group (group P), and the control group (group C), respectively. Delayed adjustment was performed once on each SRM at 4 and 6 weeks postoperatively by a masked observer. The possible length to adjust and the necessary force required for the adjustment, as well as the degree of any adhesions, were also evaluated. RESULTS: In the control group, adjustment was impossible in all of the eyes at 4 and 6 weeks postoperatively. In group P-D, adjustment was possible in 11 out of 11 eyes (11/11) 4 weeks postoperatively and in 10/11 eyes 6 weeks postoperatively. In group P, adjustment was possible in 9/11 eyes 4 weeks postoperatively and in 10/12 eyes 6 weeks postoperatively. CONCLUSIONS: Use of polyurethane film with and without SRD could delay adjustment in most eyes for up to 6 weeks postoperatively. Polyurethane is helpful for delaying adjustment in rabbit eyes until 6 weeks postoperatively without the need for frequent topical instillation of steroids.     

Anti-angiogenic activity of a homoisoflavanone from Cremastra appendiculata

A homoisoflavanone, 5,7-dihydroxy-3-(3-hydroxy-4-methoxybenzyl)-6-methoxychroman-4-one ( 1), was isolated from the bulb of Cremastra appendiculata (D. Don) Makino (Orchidaceae) as a potent inhibitor of angiogenesis. It inhibited basic fibroblast growth factor (bFGF)-induced in vitro angiogenesis and in vivo angiogenesis of the chorioallantoic membrane (CAM) of chick embryo without showing any toxicity.     

Induction of cytochrome P450s by rutaecarpine and metabolism of rutaecarpine by cytochrome P450s

Rutaecarpine is an alkaloid originally isolated from the unripe fruit of Evodia rutaecarpa. Recently, rutaecarpine has been characterized to have an anti-inflammatory activity through cyclooxygenase-2 inhibition. In the present studies, the effects of rutaecarpine on liver cytochrome P450 s (P450s) and P450 s involved in the metabolism of rutaecarpine were studied in vivo and in vitro, respectively, because the data are crucial in the early development of rutaecarpine as a new drug candidate. Oral administration to male ICR mice of rutaecarpine for 3 consecutive days induced liver P450 1A-, 2B- and 2E1-selective monooxygenase activities. The induction of P450 1A and 2B by rutaecarpine was confirmed by Western immunoblotting. When rutaecarpine was incubated with rat liver microsomes in the presence of an NADPH-generating system, five metabolites were detected by UV and mass spectral analyses. The 3-methylcholanthrene- and phenobarbital-induced microsomes greatly increased the formation of metabolites. Our present results suggest that rutaecarpine might induce P450 1A and 2B in mice, and that P450 1A and 2B might predominantly metabolize rutaecarpine in rat liver microsomes.     

Simple retrograde balloon dilation for treatment of ureteral strictures: etiology-based analysis

This study consists of an analysis of the results of simple retrograde balloon dilation in the treatment of ureteral strictures for the evaluation of the long-term efficacy of this procedure, and the factors affecting its success rate. A prospective study was performed on 43 ureteral strictures (22 malignant, 21 benign) from 37 patients treated with retrograde balloon dilation from October 1997 to May 1999. After the stricture segments were dilated, ureteral stents were indwelled uniformly for 3 weeks. Strictures were postoperatively followed up radiographically at 1, 3, 6 and 12 months, and annually thereafter. Success was defined by symptomatic and radiographic improvement. The follow-up periods ranged from 8 to 57 months (mean 41 months). The success rates of the benign strictures at 12 and 36 months were much higher than those of the malignant strictures (67 and 57% vs., 18 and 14%, p=0.0009). While 56% and 47% of the patients with strictures shorter than 2 cm were successful at 12 and 36 months, respectively, none with strictures longer than 2 cm were successful at the same follow-up periods (p=0.0002). Of the successful benign cases with a shorter segment at 12 months, 12 out of 14 (86%) showed persistent long-term successes at the 36 months follow-up. Other prognostic factors, such as sex, age, location, disappearance of a waist, dilation time and grade of hydronephrosis, were not found to influence the success rate. A multivariate analysis revealed the etiology and stricture length were the only significant prognostic factors affecting the final outcome (p=0.030 and p=0.0262, respectively, by Cox's proportional hazards model). In consideration of its minimal invasiveness and acceptable long-term outcome, simple retrograde balloon dilation is an effective treatment modality for benign ureteral stricture with a short segment (< or = 2 cm), and a shorter duration of stenting (3-weeks) is viable.     

Gentamicin-releasing urethral catheter for short-term catheterization

Urethral catheters, widely used for the drainage of the bladder, are associated with most urinary tract infections (UTIs) that account for 40% of all episodes occurring in acute-care hospitals. This study aimed to develop a gentamicin-releasing catheter that effectively prevents UTIs for short-term catheterization. For physical loading of gentamicin, the urethral catheters were coated by the simple dipping method with poly(ethylene-co-vinyl acetate) (EVA) and EVA/poly(ethylene oxide) (PEO) blends containing gentamicin. By varying the molecular weight (MW) and contents of PEO in the blends, various catheter surfaces were produced. In vitro drug release studies demonstrated that all the coated catheters exhibited sustained release up to 7 days; however, the release pattern was significantly dependant on the coating layers. Of the coated catheters, EVA/PEO (MW = 100k)-coated catheters were utilized to evaluate the antibacterial activity using an inhibition zone test, since they showed a promising drug release behavior and had PEO-rich biocompatible surfaces. In accordance with drug release behavior, EVA/PEO-coated catheters exhibited antibacterial activities for 7 days against Proteus vulgaris, Staphylococcus aureus and Staphylococcus epidermidis. These results imply that the catheters coated with EVA/PEO have a potential for short-term catheterization.     

Hemodynamic effects of gabapentin in rats

Gabapentin has been known to elicit the antinociceptive effect. However, little has been known about the effect of gabapentin on the cardiovascular system. The author's aim of this experiment was to examine the hemodynamic effects of gabapentin. Male Sprague-Dawley rats were used. Intrathecal or intracerebroventricular catheters were implanted and gabapentin was delivered through each catheter or directly into the peritoneal cavity. For hemodynamic measurements, catheters were inserted into the tail artery. Blood pressure and heart rate were measured over 60 min following administration of gabapentin. Intrathecal and intraperitoneal gabapentin did not induce significant changes of hemodynamics over the 60 min compared to the baseline value. Intracerebroventricular gabapentin increased systolic and diastolic blood pressure, but there is no statistically difference in blood pressure change according to the dose.