Neuroprotective effects of citidine-5-diphosphocholine on impaired spatial memory in a rat model of cerebrovascular dementia.

Citidine-5-diphosphocholine or citicoline (CDP-choline) is used as a neuroprotective and memory-enhancing drug in cerebral stroke, Alzheimer's disease, and other neurovascular diseases. Non-clinical studies have demonstrated the neuroprotective effects of CDP-choline in ischemic animal models. However, the relationship between the neuroprotective effect and the memory enhancing effect of CDP-choline is still unknown. No studies have demonstrated the ameliorative effect on impaired spatial memory and the suppressive effect on neuronal cell death of CDP-choline in the same model. In this study, we examined the effect of CDP-choline on impaired spatial memory and hippocampal CA1 neuronal death in rats subjected to repeated cerebral ischemia, and we compared the mechanism of CDP-choline to that of donepezil. Seven days post administration of CDP-choline (100, 300, 1000 mg/kg per day, p.o.) or donepezil increased correct choices and reduced error choices in an eight-arm radial maze task in a dose-dependent manner. Neuronal cell death of caspase-3 protein-positive neurons in the hippocampus were reduced by repeated administration of CDP-choline at the highest dose. These results suggest that CDP-choline has ameliorative effects on the impairment of spatial memory via hippocampal neuronal cell death in a rat model of cerebral ischemia.

Effects of yokukansan on anxiety-like behavior in a rat model of cerebrovascular dementia.

Behavioral and psychological symptoms of dementia (BPSD) are commonly seen in patients with dementia. Current pharmacological approaches to treatment are inadequate, despite the availability of serotonergic agents to ameliorate anxiety, one of the symptoms of BPSD. The herbal medicine yokukansan has been demonstrated to improve BPSD in a randomized, single-blinded, placebo-controlled study. However, the mechanisms of the anxiolytic effect of yokukansan have not been clarified. There are also no reports on the anxiolytic effect of yokukansan in cerebrovascular ischemia models. In this study, we examined whether rats subjected to repeated cerebral ischemia exhibited anxiety-like behavior in a plus-maze task, a light/dark box test and an open-field task. We then investigated the effect of yokukansan on anxiety-like behavior in ischemic rats. Repeated ischemia was induced by the four-vessel occlusion method in which a 10-min ischemic episode was repeated once after 60 min. Yokukansan was orally administered once a day for 14 days from 7 days before ischemia induction. The last administration was performed 1 h before the behavioral experiments. The ischemic rats showed anxiety-like behavior in all three tasks, suggesting that this rat may be a good model for anxiety in cerebrovascular dementia. Yokukansan exhibited anxiolytic effects on the anxiety-like behavior in rats subjected to repeated cerebral ischemia, and exerted antagonistic effects on the wet-dog shakes induced by 1-(2,5-dimethoxy-4-indophenyl)-2-amino propane, a serotonin receptor (5-HT(2A)) agonist. This study revealed that yokukansan shows anxiolytic effects not only in normal animals but also in cerebrovascular model rats.

Comparison of anterior and posterior corneal surface irregularity in Descemet stripping automated endothelial keratoplasty and penetrating keratoplasty.

PURPOSE: To evaluate the irregularity of the anterior and posterior cornea after Descemet stripping automated endothelial keratoplasty (DSAEK) and penetrating keratoplasty (PK). METHODS: This clinical study comprised 39 eyes: 13 consecutive eyes after DSAEK, 13 consecutive eyes after PK, and 13 age-matched normal eyes. Corneal elevation data were acquired using a rotating Scheimpflug camera 1 and 3 months after DSAEK and PK. Anterior and posterior corneal elevation data were decomposed into a set of Zernike polynomials up to eighth order. Total higher-order root mean square (RMS) and RMS from third to eighth order were calculated. The astigmatism and irregularity of the anterior and posterior surfaces were compared between DSAEK and PK. RESULTS: The regular astigmatism and tilt components of the anterior surface were significantly lower after DSAEK than after PK at 1 and 3 months (P < 0.001), whereas there was no difference in astigmatism of the posterior surface between the groups (P = 0.07, 0.22). The higher-order RMS and RMSs of third- to eighth-order components of the anterior surface were significantly larger after PK than those after DSAEK at 1 and 3 months (P < 0.01), whereas there were no significant differences between DSAEK and PK in higher-order aberration RMS and RMSs of third- to eighth-order components of the posterior surface. CONCLUSIONS: Postoperative corneal irregularity of the anterior surface was greater after PK than after DSAEK, whereas there was no significant difference in posterior surface irregularity. DSAEK is superior to PK in terms of the higher-order irregularity of the anterior surface.

Feasibility of spherical aberration correction with aspheric intraocular lenses in cataract surgery based on individual pupil diameter.

PURPOSE: To evaluate the feasibility of correcting spherical aberration with aspheric intraocular lenses (IOLs) in cataract surgery based on individual pupil diameter. SETTING: Keio University Hospital, Tokyo, Japan. METHODS: In this prospective study, eyes having cataract surgery were divided into 4 groups based on IOL type: aspheric SN (AcrySof SN60WF), aspheric ZA (Tecnis ZA9003), aspheric PY (Hoya PY-60 AD), and spherical (AcrySof Natural SN60AT). Postoperative higher-order aberrations (HOAs) of the cornea and whole eye and the pupil diameter under photopic and mesopic conditions were measured. The HOA was calculated using the individual pupil diameter. The correlation between corneal and ocular spherical aberrations and pupil diameter was evaluated. RESULTS: Each group comprised 30 eyes. Ocular spherical aberrations were significantly lower than corneal spherical aberrations under mesopic conditions in the aspheric SN group, the aspheric ZA group, and the aspheric PY group (P<.05); there was no significant difference between the aberrations in the spherical group. Linear regression showed significant correlations between postoperative corneal and ocular spherical aberrations (beta = 0.39, aspheric SN; beta = 0.38, aspheric ZA; beta = 0.58, aspheric PY; beta = 0.79, spherical). The differences in corneal and ocular spherical aberrations were significantly correlated with pupil diameter in the aspheric IOL groups but not in the spherical IOL group. CONCLUSIONS: The amount of spherical aberration correction by aspheric IOLs varied depending on IOL type and individual pupil diameter. The linear regression equation in this study may make it possible to customize postoperative ocular spherical aberration after cataract surgery.

Effect of anterior and posterior corneal surface irregularity on vision after Descemet-stripping endothelial keratoplasty.

PURPOSE: To evaluate irregularity of the anterior and posterior cornea before and after Descemet-stripping endothelial keratoplasty (DSEK) and its effect on visual acuity. SETTING: Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan. METHODS: Corneal data were acquired using a rotating Scheimpflug camera before and 1 month and 3 months after DSEK. Anterior and posterior corneal elevation data were decomposed into a set of Zernike polynomials up to the 8th order within a 4.0 mm diameter region. Total higher-order root mean square (HO-RMS) and RMS from the 3rd to 8th order were calculated. The effects of anterior and posterior surface irregularity on visual acuity were evaluated. RESULTS: This clinical study comprised 13 consecutive eyes of 12 bullous keratopathy patients. The mean best corrected visual acuity (BCVA) was 1.11 logMAR +/- 0.5 (SD) preoperatively, 0.49 +/- 0.49 logMAR 1 month postoperatively, and 0.27 +/- 0.32 logMAR at 3 months. The HO-RMS of the anterior surface 1 month (P = .040) and 3 months (P = .048) postoperatively was significantly lower than preoperatively. There were no significant differences in posterior surface HO-RMS between preoperatively and 1 month (P = .45) and 3 months (P = .054). The postoperative BCVA was significantly correlated with HO-RMS (P<.001), but not with posterior surface HO-RMS, at 3 months (P = .354). CONCLUSION: Postoperative BCVA correlated with irregularity of the anterior surface but not the posterior surface. In addition to corneal transparency, regularity of the anterior surface is an important factor in visual acuity after DSEK.

Effect of spherical aberration on visual function under photopic and mesopic conditions after cataract surgery.

PURPOSE: To evaluate the effect of spherical aberration on visual function under natural pupil conditions after cataract surgery. SETTING: Keio University Hospital, Tokyo, Japan. METHODS: This study comprised cataract patients who had cataract extraction with implantation of an acrylic intraocular lens. Preoperative and postoperative visual acuity, higher-order aberration in the whole eye, contrast sensitivity function, and pupil diameter under photopic and mesopic conditions 1 month after surgery were measured. The area under log contrast sensitivity function (AULCSF) and spherical aberration corresponding to the individual pupil diameter under photopic and mesopic conditions were evaluated. RESULTS: One hundred seven eyes of 79 patients (30 men, 49 women; mean age 68.0 years +/- 9.6 [SD]) were evaluated. The mean pupil diameter was 2.9 +/- 0.50 mm under photopic conditions and 3.6 +/- 0.57 mm under mesopic conditions. The mean spherical aberration was 0.03 +/- 0.04 mum (range -0.12 to 0.34 mum) under photopic conditions and 0.05 +/- 0.10 mum (range -0.14 to 0.55 mum) under mesopic conditions. The postoperative AULCSF without glare under photopic conditions was significantly negatively correlated with spherical aberration (P = .014). The postoperative AULCSF with and without glare under mesopic conditions was significantly negatively correlated with spherical aberration (P<.001 and P = .01, respectively). CONCLUSIONS: Postoperative spherical aberration had a significant effect on visual function under photopic and mesopic conditions. This result indicates that reduced postoperative spherical aberration improves postoperative visual function under photopic and mesopic conditions.

Hemophagocytic lymphohistiocytosis in very young infants.

We report three cases of hemophagocytic lymphohistiocytosis (HLH) in infants within the first 6 weeks of life. Diagnosis of HLH was made early after symptoms started. All three cases were successfully treated with dexamethasone and none relapsed, indicating that not all cases of HLH in very young infants are familial.