Changes in Peripheral Anterior Chamber Depth of a Case of Relapsing Polychondritis with Recurrent Secondary Angle Closure Glaucoma§

A case of relapsing polychondritis showed IOP elevations three times during the follow-up due to the angle-closure mechanism. The peripheral anterior chamber depth (ACD) showed a good correlation with IOP elevation, but central ACD did not. The peripheral ACD could be more related to IOP elevation than central ACD

Pharmacological mechanisms, clinical effectiveness, and side-effects of prostaglandin analogues as anti-glaucoma agents

Prostaglandin (PG)-related ophthalmic solutions, which only recently became available for clinical use, are currently the most widely used solutions in the treatment of glaucoma, because they have excellent ocular hypotensive effects with little adverse effects. With respect to the pharmacological mechanism of action of these solutions, the mechanism of intraocular pressure (IOP) reduction for latanoprost, the first drug in this class to become available, is to promote the outflow of aqueous humor through the uveoscleral route, an important aqueous humor outflow tract. Molecular and cellular studies have shown that latanoprost affects the extracellular matrix metabolism in the uveoscleral route. For other PG-related ophthalmic solutions, there is no consensus opinion on their effects on the aqueous humor outflow tract, and how they reduce the IOP remains largely unclear. The docosanoid, isopropyl unoprostone, has excellent ocular hypotensive effects, despite having extremely low affinities to the known PG receptors. Many basic and clinical studies have demonstrated that PG-related ophthalmic solutions themselves cause not only a decrease in the IOP, but also induce endogenous PGs which could lead to secondary effects that may account in part for the IOP reduction. PG-related ophthalmic solutions have essentially no clinically important systemic adverse effects, but often have local adverse effects. The most characteristic is the pigment deposition in the iris or eyelid. Corneal epitheliopathy is also relatively common. In addition, as an adverse effect that affects vision, cystoid macular edema can be seen. Current studies are aimed at elucidating the mechanisms of development of these adverse effects, and thus to establish measures to prevent them. We compare the mechanisms of action of PG-related ophthalmic solutions and review the adverse effects and their mechanisms.Biomedical Reviews 2002; 13: 17-27

Effect of Bakumondo-to on cytochrome P450 activities in rat liver microsomes

AbstractBakumondo-to is a traditional herbal medicine. It has been widely used for the treatment of chronic airway diseases. Recently, it was reported that several herbal medicines affected cytochrome P450 (CYP). However, there is little information about the effects of Bakumondo-to on CYP activities. In this study, we evaluated the effects of Bakumondo-to on CYP activities in rat liver microsomes. Rats were orally treated twice a day with Bakumondo-to at doses of 2.0g/kg body weight/day for 4days. CYP activities were determined in liver microsomes isolated from treated rats. CYP1A2, CYP2C, and CYP3A activities were measured using their specific substrates [7-methoxyresorufin, 7-methoxy-4-(trifluoromethyl)-coumarin, and 7-benzyloxyquinoline, respectively]. Bakumondo-to decreased CYP1A2 activity by 42.5±7.8%, increased CYP2C activity by 158.0±29.6%, and decreased CYP3A activity to 81.5±7.8% of the control level. Activities were expressed as percentages of the control.Bakumondo-to induced CYP2C activity and decreased CYP1A2 activity; it may cause drug-herbal interactions. It is suggested that combinations of Bakumondo-to and drugs that are metabolized by CYP1A2 and CYP2C should be carefully used in clinical settings

Validating Variational Bayes Linear Regression Method With Multi-Central Datasets.

PurposeTo validate the prediction accuracy of variational Bayes linear regression (VBLR) with two datasets external to the training dataset.MethodThe training dataset consisted of 7268 eyes of 4278 subjects from the University of Tokyo Hospital. The Japanese Archive of Multicentral Databases in Glaucoma (JAMDIG) dataset consisted of 271 eyes of 177 patients, and the Diagnostic Innovations in Glaucoma Study (DIGS) dataset includes 248 eyes of 173 patients, which were used for validation. Prediction accuracy was compared between the VBLR and ordinary least squared linear regression (OLSLR). First, OLSLR and VBLR were carried out using total deviation (TD) values at each of the 52 test points from the second to fourth visual fields (VFs) (VF2-4) to 2nd to 10th VF (VF2-10) of each patient in JAMDIG and DIGS datasets, and the TD values of the 11th VF test were predicted every time. The predictive accuracy of each method was compared through the root mean squared error (RMSE) statistic.ResultsOLSLR RMSEs with the JAMDIG and DIGS datasets were between 31 and 4.3 dB, and between 19.5 and 3.9 dB. On the other hand, VBLR RMSEs with JAMDIG and DIGS datasets were between 5.0 and 3.7, and between 4.6 and 3.6 dB. There was statistically significant difference between VBLR and OLSLR for both datasets at every series (VF2-4 to VF2-10) (P < 0.01 for all tests). However, there was no statistically significant difference in VBLR RMSEs between JAMDIG and DIGS datasets at any series of VFs (VF2-2 to VF2-10) (P > 0.05).ConclusionsVBLR outperformed OLSLR to predict future VF progression, and the VBLR has a potential to be a helpful tool at clinical settings

Efficacy and Safety of Switching Prostaglandin Analog Monotherapy to Tafluprost/Timolol Fixed-Combination Therapy

Purpose. To assess the efficacy and safety of switching from prostaglandin analog (PGA) monotherapy to tafluprost/timolol fixed-combination (Taf/Tim) therapy. Subjects and Methods. Patients with primary open-angle glaucoma, normal-tension glaucoma, or ocular hypertension who had received PGA monotherapy for at least 3 months were enrolled. Patients were examined at 1, 2, and 3 months after changing therapies. Subsequently, the patients were returned to PGA monotherapy. The examined parameters included intraocular pressure (IOP) and adverse events. A questionnaire survey was conducted after the switch to Taf/Tim therapy. Results. Forty patients with a mean age of 66.5 ± 10.3 years were enrolled; 39 of these patients completed the study protocol. Switching to Taf/Tim significantly reduced the IOP from 18.2 ± 2.6 mmHg at baseline to 14.8 ± 2.5 mmHg at 1 month, 15.2 ± 2.8 mmHg at 2 months, and 14.9 ± 2.5 mmHg at 3 months (P<0.001). Switching back to the original PGA monotherapy returned the IOP values to baseline levels. Taf/Tim reduced the pulse rate insignificantly. No significant differences were observed in blood pressure, conjunctival hyperemia, or corneal adverse events. A questionnaire showed that the introduction of Taf/Tim did not significantly influence symptoms. Conclusions. Compared with PGA monotherapy, Taf/Tim fixed-combination therapy significantly reduced IOP without severe adverse events

Quantification of neuropathological findings by image data for the diagnosis of dementia in forensic autopsy cases

The aim of the present study was to quantify neuropathological findings using image analysis software for the diagnosis of dementia in deceased who underwent forensic autopsy. Of the autopsies performed within 48 hours of death and excluding those of patients with head injury, thermal injury, heat stroke, or intracranial lesions, 8 were of autopsy cases clinically diagnosed with dementia and thus included in the dementia group (D). The non-dementia group (non-D) consisted of 6 deceased without dementia. To compare the D and non-D groups, 6 regions and 7 types of pathological findings were observed semi-quantitatively using 4 conventional stainings. Quantitative analysis of collected image data was performed using image analysis software. Semiquantitative analysis of senile plaques and neurofibrillary tangles was performed with Bielschowsky-Hirano’s silver staining image data. An easy, simple, and effective quantification method of the pathological findings was achieved. However, no significant differences were observed between the two groups, and diagnosis of dementia by the quantification of pathological findings was not successful. Diagnosis of dementia using image data may be possible in future studies with an increased number of autopsies, and by utilizing staining techniques with higher specificity and sensitivity, such as immunohistochemical staining

Organ distribution of p-cresol in HD patients

Background : p-Cresol concentrations are high in the blood of hemodialysis (HD) patients. However, its organ distribution has not yet been investigated in detail. We herein report the distribution of p-cresol in HD patients from forensic autopsy cases. Methods : p-Cresol was measured in the blood, urine, lungs, liver, and kidneys from 4 HD and 4 non-HD cases. Samples were extracted with p-cresol-d8 (internal standard), derivatized, and injected on the GC-MS. Results and Discussion : The total urinary p-cresol/Cr was 79.73 ng/ml in HD cases, which was 16-fold higher than that in non-HD cases. p-Cresol in the blood and kidneys were 30-fold higher or more at 11.92 and 13.08 µg/mL(g), respectively. p-Cresol in the liver and lungs were approximately 20-fold higher at 4.82 and 9.99 µg/g, respectively. p-Cresol was markedly increased in not only the blood, but also the urine and organs of HD cases. The distribution of p-cresol in the blood, urine, and organs differed between HD and non-HD cases. In HD cases, the percentages of conjugated (C) and protein-bound conjugated (PC) urinary p-cresol were 57 and 41%, respectively. C and PC p-cresol was 66% and 25% in the kidneys, respectively, and similar results were obtained in the lungs