Risk Factors for Elevated Intraocular Pressure After Trans-Tenon Retrobulbar Injections of Triamcinolone

Purpose

To determine the risk factors that induce an elevation of intraocular pressure (IOP) after trans-Tenon retrobulbar injections of triamcinolone acetonide.

Methods

We retrospectively reviewed the medical records of 49 consecutive patients (49 eyes) with choroidal neovascularization or diffuse diabetic macular edema who had received one trans-Tenon retrobulbar injection of triamcinolone acetonide (20?mg) between June 2003 and September 2004, while being treated at Kagawa University Hospital or Okayama Saiseikai General Hospital. Diabetes mellitus had been diagnosed in ten of the patients. Steroid responders were defined as having a relative increase in intraocular pressure (IOP) of >6?mmHg and an absolute IOP >20?mmHg with an anatomically open anterior chamber angle. The mean follow-up time was 4.2 ± 0.2 months (range, 3–6 months).

Results

Nine patients were responders and 40 patients were nonresponders. The elevation of the IOP occurred 1 to 4 weeks after the injection. The only preoperative predictive factor for the steroid responders was the presence of diabetes mellitus (multiple logistic regression analysis, odds ratio = 32.78, P = 0.006). After topical glaucoma medication, the IOP returned to acceptable levels in all responders.

Conclusions

Our results suggest an association between diabetes mellitus and elevated IOP after a trans-Tenon retrobulbar triamcinolone acetonide injection.?Jpn J Ophthalmol 2006;50:235–238 © Japanese Ophthalmological Society 2006     

Long-term Retention of Dye After Indocyanine Green-Assisted Internal Limiting Membrane Peeling

Purpose

To evaluate dye retention in the fundus after indocyanine green (ICG)-assisted internal limiting membrane peeling.

Methods

Ten eyes with stage 3 or 4 nondiabetic idiopathic macular hole (MH group) and six eyes with diffuse diabetic macular edema (DM group) were studied. The fundus was examined with 780-nm infrared illumination by a scanning laser ophthalmoscope (SLO) after ICG-assisted internal limiting membrane peeling. The postoperative follow-up period ranged from 6 to 12 months (mean ± SD, 3.7 ± 2.6 months).

Results

Fluorescence from ICG was detected in all studied eyes in both groups up to 6 months after surgery. At 9 months after surgery, ICG fluorescence was visible in all eyes of the DM group, but in only one-third of eyes of the MH group. No fluorescence was detected in fellow eyes that had not been operated on.

Conclusion

The present study using SLO revealed that ICG remains in the fundus for over 6 months after surgery. The results also suggested that a longer time might be required for dye clearance from the diabetic retina than from the nondiabetic retina.?Jpn J Ophthalmol 2006;50:349–353 © Japanese Ophthalmological Society 2006     

Distribution of DJ-1, Parkinson's disease-related protein PARK7, and its alteration in 6-hydroxydopamine-treated hemiparkinsonian rat brain

DJ-1 has multiple functions and its dysfunction may be linked to the onset of familial Parkinson's disease PARK7. However, the function and distribution of DJ-1 is unclear. In this study, we determined DJ-1 distribution and change after intranigral injection of 6-hydroxydopamine (6-OHDA). Although distribution of DJ-1 immunoreactivity was not changed in cerebral cortex and striatum, 6-OHDA caused increase of DJ-1 in the particulate fraction and decrease in the cytosolic fraction in substantia nigra. At that time, DJ-1 shifted to acid forms. These results suggest that distributional changes, translocation, and acidic shift of DJ-1 may be compensatory responses to protect against 6-OHDA-induced oxidative stress.     

Effect of amiodarone on the serum concentration/dose ratio of metoprolol in patients with cardiac arrhythmia

Amiodarone has pharmacokinetic interactions with a number of therapeutic drugs, including warfarin, phenytoin, flecainide, and cyclosporine. Metoprolol is mainly metabolized by CYP2D6, and desethylamiodarone, a metabolite of amiodarone, has a markedly greater inhibitory effect on CYP2D6 than amiodarone. Therefore, the goal of this study was to evaluate the effect of amiodarone and desethylamiodarone on the serum concentration/dose ratio (C/D) of metoprolol in 120 inpatients with cardiac arrhythmias that received either metoprolol and amiodarone (MET+AMD group, n=30) or metoprolol alone (MET group, n=90). The ratio of administered metoprolol was compared between the MET and the MET+AMD groups. The dose of metoprolol and patient age were significantly higher in the MET group when compared with the MET+AMD group (1.00+/-0.480 versus 0.767+/-0.418 mg/kg/day, p<0.050; 68.6+/-10.6 versus 57.6+/-14.1 years, p<0.001, respectively), but the C/D ratio was significantly lower in the MET group than in the MET+AMD group (90.8+/-64.0 versus 136+/-97.8, p<0.01). Furthermore, a significant correlation was found between the C/D ratio and desethylamiodarone concentration (n=30, r=0.371, p<0.01). The results suggest that there is a significant interaction between amiodarone and metoprolol via desethylamiodarone-induced inhibition of CYP2D6. Therefore, careful monitoring of metoprolol concentrations/bioactivity of CYP2D6 is required in the context of co-administration of amiodarone and metoprolol.     

Morphological change by overexpression of D385A dominant negative presenilin 1 in human neuroblastoma SH-SY5Y cells

Presenilin 1 (PS1) is a multifunctional protein, and its mutations are highly related to familial Alzheimer's disease (AD). In this study, we examined the effects of PS1 overexpression on neuronal morphology using SH-SY5Y cells. Overexpression of dominant-negative D385A PS1 induced morphological change and impairment of neurite formation, while those of wild-type and pathogenic P117L mutant PS1 did not change cellular morphology compared with native cells. Moreover, filopodium-formation-related proteins were decreased only in cells overexpressing D385A PS1. Therefore, PS1 may be involved in neuritogenesis and morphological change in SH-SY5Y cells, and P117L mutation may linked to AD by different mechanisms.     

APC gene methylation is inversely correlated with features of the CpG island methylator phenotype in colorectal cancer

The notion of a CpG island methylator phenotype (CIMP) was proposed to describe a subset of colorectal cancers (CRC) displaying frequent and concordant methylation of CpG islands located within gene promoter regions. Some workers have failed to observe associations between CIMP and specific clinicopathological features of CRC, possibly because of the choice of genes used to define this phenotype. The aim of the current study was to determine whether the aberrant methylation of 6 genes implicated in CRC development was associated with the same phenotypic features of this tumour type. The MethyLight assay was used to provide quantitative estimates of MLH1, P16, TIMP3, P14, DAPK and APC methylation levels in 199 unselected colorectal tumours. The methylation of MLH1, P16, TIMP3 and P14 was highly concordant (p < 0.0001 for each pair) but that of DAPK and APC was not. An inverse association was observed between the methylation of APC and TIMP3 (p = 0.004). Methylation of the MLH1, P16, TIMP3 and P14 genes was associated with tumour infiltrating lymphocytes (p < 0.05), microsatellite instability (p < 0.001), BRAF mutation (p < 0.0001) and elevated concentrations of the methyl group carriers tetrahydrofolate (THF) and 5,10-methylene THF (p < 0.05). In contrast, APC methylation was associated with wildtype BRAF (p = 0.003) and with lower concentrations of methyl group carriers (p < 0.05). These findings highlight the importance of gene selection in studies that aim to characterize the biological features and clinical behaviour of CIMP+ tumours.     

Buformin suppresses the expression of glyceraldehyde 3-phosphate dehydrogenase

The biguanides metformin and buformin, which are clinically used for diabetes mellitus, are known to improve resistance to insulin in patients. Biguanides were reported to cause lactic acidosis as a side effect. Since the mechanism of the side effect still remains obscure, we have examined genes whose expression changes by treating HepG2 cells with buformin in order to elucidate the mechanisms of the side effect. A subtraction cDNA library was constructed by the method of suppressive subtractive hybridization and the screening of the library was performed with cDNA probes prepared from HepG2 cells treated with or without buformin for 12 h. The expression of the gene and the protein obtained by the screening was monitored by real-time RT-PCR with specific primers and Western blotting with specific antibody. The amounts of ATP and NAD+ were determined with luciferase and alcohol dehydrogenase, respectively. We found that expression of the glyceraldehyde 3-phosphate dehydrogenase (GAPD) gene was suppressed by treating HepG2 cells with 0.25 mM buformin for 12 h as a result of the library screening. The decrease in the expression depended on the treatment period. The amount of GAPD protein also decreased simultaneously with the suppression of the gene expression by the treatment with buformin. The amount of ATP and NAD+ in the HepG2 cells treated with buformin decreased to 10 and 20% of the control, respectively. These observations imply that the biguanide causes deactivation of the glycolytic pathway and subsequently the accumulation of pyruvate and NADH and a decrease in NAD+. Therefore, the reaction equilibrium catalyzed by lactate dehydrogenase leans towards lactate production and this may result in lactic acidosis.     

Correlation between plasma glucagon-like peptide 2 levels and proliferative makers in small intestinal injury in rats induced by methotrexate administration

Glucagon-like peptide 2 (GLP-2) is a potent intestinal epithelium-specific growth factor that has been shown to reduce the severity of inflammatory disorders of the intestine in rodent models. We examined whether a relationship exists between plasma level of GLP-2 and the degree of intestinal injury induced by chemotherapeutic agents in the rat. Methotrexate (MTX) was administrated orally for 6 consecutive days at doses of 1.25, 2.5, and 5.0 mg/kg body weight per day. Mucosal samples of rat duodenum, jejunum, and ileum were used for assessment of mucosal weight, DNA and protein content. Plasma GLP-2 levels were measured on day 8. MTX significantly reduced body weight. The values of all indices tended to decrease in all segments with increases in MTX dose. Plasma GLP-2 levels were significantly higher in the MTX 2.5 mg/kg/d group (p<0.05) and the MTX 5.0 mg/kg/d group (p<0.01) than in the control group. Correlations were found between plasma GLP-2 levels and mucosal weight, DNA and protein content. We concluded that plasma GLP-2 levels reflect the degree of intestinal injury following MTX administration in this preclinical model.     

Comparison of activity level in daily life with heart rate: Application to elderly persons of different ambulatory abilities

Objectives Normal activity monitoring methods are mainly useful for relatively healthy and ablebodied people, but are not necessarily appropriate for elderly persons who may have difficulty in walking, or for the frail who may be bedridden. The purpose of this study was to examine 24-hour heart rate recording for the comparison of activity levels in daily life of elderly persons of different ambulatory abilities. Methods Forty-two elderly females (mean, 82.1 years old) volunteered to participate in this study. The subjects were divided into four groups on the basis of their ambulatory status, and their 24-hour heart rate recordings were compared with their results of activity assessments. Results The results of activity assessments showed a tendency to decrease as the ambulatory ability of the group decreased. The “total heart beats”, calculated as the sum of all heart rates over 24 hours, were almost the same among the four groups, and therefore did not show a similar tendency. However, the “total excess-beats product (TEBP)” correlated with the results of activity assessments. TEBP was calculated as the sum of all differences in beats between each heart rate in 24 hours and the mean heart rate during sleeping at night. Therefore, TEBP may reflect a more active state than the bedridden state. Conclusions These results suggest that comparison of activity levels in daily life using 24-hour heart rate recording might be possible by the calculation of TEBP, and that this method might be useful for the comparison of the activity levels of elderly persons of diffent ambulatory abilities. Formerly: Department of Public Health, Hirosaki University School of Medicine, Hirosaki, Japan Formerly: Department of Public Health, Hirosaki University School of Medicine, Hirosaki, Japan Formerly: Department of Public Health, Hirosaki University School of Medicine, Hirosaki, Japan