Probucol decreases mevalonate pyrophosphate decarboxylase in the rat liver

It is known that cholesterol biosynthesis in the liver is inhibited by probucol. This inhibition by probucol is caused at least in part by a decrease in 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase activity. In this study, we examined serum cholesterol and the change in the activity or protein level of mevalonate pyrophosphate decarboxylase (MPD), which is involved in cholesterol biosynthesis, in the livers of rats fed probucol. The results indicated that serum cholesterol, MPD activity and MPD protein were decreased by 70, 50 and 60% by probucol, respectively, as compared with those in rats fed normal chow. These data show for the first time that probucol decreases the level of an enzyme involved in cholesterol biosynthesis other than HMG-CoA reductase.     

Peroxisome proliferative drugs do not induce an increase of rat mevalonate pyrophosphate decarboxylase

To determine whether or not the expression of mevalonate pyrophosphate decarboxylase (MPD) depends on the proliferation of peroxisomes, we examined change in the protein level of MPD in the crude extract, the cytosol and the peroxisome-enriched fraction of the livers of rats administered peroxisome proliferative drugs. No increase of MPD was observed in any of these fractions. These data suggest that the expression of MPD is independent of the proliferation of peroxisomes and may be maintained via a specific regulatory mechanism different from that of the expression of peroxisome proliferator-activated receptor alpha.     

Evaluation of skin barrier function using direct current III: effects of electrode distance,boundary length and shape

The objective of this study was to propose a suitable electrode disposition and shape for iontophoretic drug delivery systems in consideration of a reduction in skin barrier function and a distribution of current density. The reduction in barrier function was evaluated with our proposed method, which measured the resistance in the short term. The distribution was estimated using an electromagnetic waves analysis program. Using rectangular electrodes, effects of distance between electrodes and boundary length of the electrode on the barrier function were examined. A distance of 2 mm decreased the barrier function effectively. The barrier function was reduced with increasing electrode boundary length. Furthermore, a surrounded square type electrode was more effective in the reduction of barrier function than a paired square type. With respect to the surrounded type electrodes, both square and circle types decreased the barrier function. However, percutaneous absorption using the circle type electrode was greater than with the square type. These phenomena are attributed to not only the electrode boundary length but also the homogeneous distribution of current density. Therefore, the surrounded circle type electrode was suitable for iontophoretic transdermal drug delivery systems.     

Relationship between human leukocyte antigen status and proliferative diabetic retinopathy in patients with younger-onset type 1 diabetes mellitus

PURPOSE: To investigate the relationship between human leukocyte antigen (HLA) status and proliferative diabetic retinopathy (PDR) to assess the genetic basis of PDR in younger type 1 diabetic patients. DESIGN: Retrospective, nonrandomized, comparative trial. METHOD: Patients who were diagnosed with type 1 diabetes under 30 years of age (range, 13-28) and had a disease duration of more than 10 years were studied. The patients were divided into two groups: 30 patients who had undergone vitreous surgery younger than 40 years old (the PDR group) and 50 patients without retinopathy (the non-DR group). The duration of diabetes and the level of glycemic control were matched between the two groups. The control group consisted of 50 healthy patients. HLA-A, -B, -C, -DR, and -DQ typing of blood samples was done using the standard microcytotoxicity method. RESULTS: The frequency of HLA-B62, Cw4, and DQ4 was significantly higher in the PDR group than in the non-DR group (P =.0020, P =.048, and P =.0026, respectively). The Cw4-DR4-DQ4 haplotype frequency was significantly higher in the PDR group than in the control group and the non-DR group (P =.0059). CONCLUSIONS: Our results suggests that HLA-B62, Cw4, and DQ4 may be useful for predicting the prognosis of retinopathy in patients with younger-onset type 1 diabetes.     

A case of occult macular dystrophy accompanying normal-tension glaucoma

PURPOSE: To present a case of occult macular dystrophy accompanying normal-tension glaucoma. DESIGN: Observational case report. METHODS: Visual function and ophthalmoscopic and electroretinographic findings in a 56-year-old man suffering from gradually progressive photophobia and visual dysfunction were followed up over 4 years. RESULTS: Best-corrected visual acuity was below 20/200, and intraocular pressures remained in the low teens in both eyes. A wedge-shaped visual field defect in the right eye, corresponding to the enlarged disk cupping, and a relative central scotoma in the left were detected. Ophthalmoscopy and fluorescein angiography detected no apparent abnormality at the macular region in either eye. Severely attenuated multifocal electroretinographic responses were recorded from only the central areas, with normal full-field responses. CONCLUSION: Clinicians must look for additional pathologic conditions in patients with normal-tension glaucoma who have unexplained central visual dysfunction.     

Corneal thickness as a risk factor for visual field loss in patients with preperimetric glaucomatous optic neuropathy

PURPOSE: To determine whether central corneal thickness (CCT) is a risk factor for visual field loss development among patients diagnosed with preperimetric glaucomatous optic neuropathy (GON). DESIGN: Observational cohort study. METHODS: The study included 98 eyes of 98 patients with GON, with a mean follow-up time of 4.3 +/- 2.7 years. Diagnosis of GON was based on masked assessment of optic disk stereophotographs. All patients had normal standard automated perimetry visual fields at baseline. Criteria for visual field abnormality were derived from a prior study. Several clinical factors (CCT, intraocular pressure, vertical cup-to-disk ratio, refraction, age, gender, family history of glaucoma, high blood pressure, cardiovascular disease, and migraine) were investigated to ascertain whether there is an association with development of repeatable visual field loss. Cox proportional hazards models were used to obtain hazard ratios (HR) and identify factors that predicted which individuals developed glaucomatous visual field loss during the follow-up period. RESULTS: Thirty-four patients (35%) developed repeatable visual field abnormality during follow-up. In multivariate analysis, risk factors that predicted the development of visual field loss were a thinner CCT (adjusted HR = 1.62/40 microm thinner; P =.023; 95% confidence interval [CI]: 1.07-2.45), higher baseline intraocular pressure (adjusted HR = 1.07/mm Hg; P =.022; 95% CI: 1.01-1.14), and larger baseline vertical cup-to-disk ratio (adjusted HR = 1.63/0.1 larger; P =.009; 95% CI: 1.13-2.35). The mean +/- standard deviation CCT of GON patients who developed visual field loss was 543 +/- 36 microm compared with 565 +/- 35 microm of those who did not develop visual field abnormalities (P =.005, Student t test). CONCLUSIONS: Central corneal thickness is a risk factor for development of visual field loss among patients diagnosed with preperimetric GON. It is important to consider CCT when establishing target intraocular pressure of patients with GON.     

Antigenicity of porcine cornea as xenograft

PURPOSE: To investigate the antigenicity of porcine corneal stroma as xenograft to man. METHODS: The localization of alpha-gal epitope in the porcine eye was determined using biotinylated Griffonia simplicifolia 1 isolectin B4. Porcine corneal stromal was inserted into corneal stromal pockets of cynomolgus monkeys. Immunohistochemistry was performed to analyze the immunological reaction in the monkey. RESULTS: Immunohistochemistry showed no alpha-gal epitope in the porcine cornea except for several keratocytes in the anterior-most part. Haze and keratic precipitates developed in two corneas out of three corneas that were followed up until 6 months after the surgery. In these two corneas, infiltrating cells included CD4+, CD8+, or HAM56+ cells, suggesting that haze and keratic precipitates were induced by cellular rejection to porcine corneal stroma. CONCLUSIONS: Porcine corneal stroma induces no hyperacute rejection but mild cellular rejection when transplanted in the cornea of cynomolgus monkeys.     

RDH5 gene mutations and electroretinogram in fundus albipunctatus with or without macular dystrophy: RDH5 mutations and ERG in fundus albipunctatus

The aim of this study was to analyze the RDH5 gene in patients with fundus albipunctatus with and without macular dystrophy, and correlate the identified mutations with the electrophysiological results. Twenty-one patients from 19 unrelated Japanese families with fundus albipunctatus were examined. Ten unrelated patients had macular dystrophy. In 18 patients, either a homozygous or a compound heterozygous mutation in the RDH5 gene was identified. The bright-flash, mixed rod-cone ERG had a negative configuration with reduced a-wave amplitudes after a short period of dark-adaptation (20 or 30 min). After a prolonged dark-adaptation period (2 or 3 h), the waveform attained normal amplitudes in patients without macular dystrophy but the a-waves were still subnormal in patients with macular dystrophy. The photopic ERG responses were significantly reduced in patients with macular dystrophy, indicating that they also had cone dystrophy. The photopic ERGs were reduced in only some of the patients without macular dystrophy. In patients without macular dystrophy, the scotopic b-wave amplitudes were nonrecordable or significantly reduced after a short dark-adaptation period but then improved to normal levels. However, they did not fully recover in some patients with macular dystrophy. Three patients with macular dystrophy in whom a RDH5 gene mutation could not be detected by our routine method had atypical ERG responses. We conclude that RDH5 gene mutations cause a progressive cone dystrophy or macular dystrophy as well as night blindness. The clinical phenotype including electrophysiological responses varied among patients with the RDH5 gene mutations.