Pathology of embolic debris in carotid artery stenting.

BACKGROUND: The relationship between magnetic resonance (MR) plaque imaging and the pathology of distal embolic debris is unknown. We aimed to evaluate the relationship between the pathology of embolic debris in the embolic filter during carotid artery stenting (CAS), MR plaque imaging, and new ischemic lesions on diffusion-weighted imaging (DWI). METHOD: We prospectively reviewed the 36 patients who underwent CAS using a filter-type embolic protection device. Pathology of debris was categorized into thrombosis, inflammatory cells, elastic fiber, and calcification. We compared the clinical parameters, MR plaque imaging, and pathological characteristics of the embolic debris retained in the filter during CAS on univariate analysis. RESULTS: Eleven patients had and 25 patients did not have new lesion on DWI. All of DWI-high lesions were identified in affected side middle cerebral artery territory. Embolic debris was microscopically confirmed in 28 patients (78%); thrombosis in 11 (31%), inflammatory cells in 13 (36%), elastic fiber in 12 (33%), and calcification in 9 (25%). Proportion of asymptomatic carotid stenosis, intra-operative bradycardia/hypotension, and inflammatory cells of debris were significantly higher in patients with new DWI-high lesions. There was no significant relationship between the pathological characteristics and MR plaque imaging of distal embolic debris. CONCLUSIONS: Our study showed that new DWI-high lesions might be influenced by types of debris in the filter. The need for future studies specifically examine the association of pathology of debris and findings of MR plaque imaging with new DWI-high lesions during CAS is emphasized.

Arterial stiffness as a risk factor for cerebral aneurysm.

OBJECTIVES: A low ankle-brachial index (ABI) is associated with increased mortality and risk of myocardial infarction and stroke in the general population. Arterial stiffness can be assessed non-invasively by the measurement of brachial-ankle pulse wave velocity (PWV), a simple and reproducible method. Because the importance of ABI and baPWV in the pathogenesis of cerebral aneurysms remains uncertain, we aimed to measure ABI and baPWV in patients with intracranial saccular and dissecting aneurysms to clarify whether these aneurysms are associated with arterial stiffness and atherosclerosis. MATERIALS AND METHODS: We prospectively investigated 78 patients diagnosed with intracranial saccular (n = 66) and dissecting (n = 12) aneurysms. The control group consisted of an age- and gender-matched normal population. We compared the clinical characteristics in patients with intracranial saccular aneurysms and controls, those with intracranial dissecting aneurysms and controls, and those who had cerebral aneurysms with and without subarachnoid hemorrhage. We also compared ABI and baPWV among saccular aneurysm locations and evaluated the correlation between the number of saccular aneurysms and ABI and baPWV. RESULTS: Multivariate logistic regression analysis shows that hypertension and higher baPWV (>1400 cm/s) are significantly associated with saccular aneurysms. Simple regression analysis revealed no correlation between the number of saccular aneurysms and ABI (r = -0.064, P = 0.611), and baPWV (r = 0.007, P = 0.956). CONCLUSIONS: The baPWV was associated with intracranial saccular aneurysms even after adjustment of hypertension and smoking. Assessment of the baPWV may aid the evaluation of the intracranial saccular aneurysm and the development of strategies for screening patients with intracranial saccular aneurysms.

The utility of patent ductus arteriosus closure with hemostatic clip in dogs.

This study investigated the utility of patent ductus arteriosus (PDA) closure with hemostatic clip by comparing with traditional PDA closure. Medical records of 51 dogs with surgical closure of PDA were reviewed and retrospective study was conducted. 29 dogs were treated by procedure with hemostatic clip (Group HC), and 22 dogs were treated by surgical ligation (Group SL). Data pertaining to breed, sex, age and body weight at the time of surgery, echocardiographic minimal ductal diameter, duration of surgery, hemostatic clip size, echocardiographic findings, hemor-rhage, residual ductal flow and recanalization were collected from records. The results showed that procedure with hemostatic clip had been selected in lighter dogs than traditional PDA closure. Duration of surgery performed only hemostatic clip technique was significantly shorter than that in group SL. Preoperative LVIDd, E-wave and FS were significantly lower than postoperative ones. As regard all parameters, the differences between pre- and postoperative periods were not significantly different between group HC and group SL. Hemorrhage, residual ductal flow, and recanalization were not significantly different in both groups. The present study showed that procedure with hemostatic clip is beneficial in that it is available in smaller dogs and can make shorter operation duration than traditional PDA closure. Moreover, the procedure is effective for the resolution of volume overload of the left atrium and ventricle in short-term outcome. Complications including hemorrhage, residual ductal flow and recanaliza-tion were not significantly different with both techniques.

DNA methylation is a critical cell-intrinsic determinant of astrocyte differentiation in the fetal brain.

Astrocyte differentiation, which occurs late in brain development, is largely dependent on the activation of a transcription factor, STAT3. We show that astrocytes, as judged by glial fibrillary acidic protein (GFAP) expression, never emerge from neuroepithelial cells on embryonic day (E) 11.5 even when STAT3 is activated, in contrast to E14.5 neuroepithelial cells. A CpG dinucleotide within a STAT3 binding element in the GFAP promoter is highly methylated in E11.5 neuroepithelial cells, but is demethylated in cells responsive to the STAT3 activation signal to express GFAP. This CpG methylation leads to inaccessibility of STAT3 to the binding element. We suggest that methylation of a cell type-specific gene promoter is a pivotal event in regulating lineage specification in the developing brain.

Retinal concentration and protective effect against retinal ischemia of nilvadipine in rats.

PURPOSE: Several calcium entry blockers have neuroprotective effects on cellular damage in the brain induced by ischemia. The purpose of this study was to determine whether nilvadipine (NID) crosses the blood-retinal barrier, and if so, whether it can then protect the photoreceptors against retinal ischemia-reperfusion injury. METHODS: Rats received an intramuscular injection of 1 mg/kg of NID and nifedipine (NIF), and the retinal and serum concentrations were measured. Ischemia was induced by raising the intraocular pressure for 45 minutes. Twenty-four hours after the reperfusion, the number of TUNEL positive cells and retinal ganglion cells (RGCs) were counted, and the thickness of the retina was measured. RESULTS: After 60 minutes, the concentration of NID, but not NIF, was higher in retina than in the serum. The number of TUNEL-positive cells was fewer and the reduction in the number of RGCs and the thickness of retina was less in the eyes that had received NID than controls. CONCLUSIONS: The findings show that NID has high permeability to retina compared with NIF, which has less fat solubility than NID, and neuroprotective effect to retinal cells. NID might be useful for the treatment of glaucoma or other retinal diseases that have some relation to apoptosis.

Effect on partial pressure of oxygen in arterial blood in percutaneous vertebroplasty.

BACKGROUND AND PURPOSE: The purpose of this study is to estimate the change in partial pressure of oxygen (Pao(2)) during percutaneous vertebroplasty and also to examine the factors related to the change in Pao(2). MATERIALS AND METHODS: We retrospectively reviewed preprocedural and postprocedural Pao(2) of 59 consecutive patients who underwent percutaneous vertebroplasty between November 2003 and April 2005 (11 men and 48 women; age range, 50-93; mean age, 75 years). Fifty-four patients were treated for osteoporosis-related fractures and 5 had malignant disease. Percutaneous vertebroplasty was performed in a conventional manner under local anesthetics and conscious sedation. Preprocedural and postprocedural blood drawing was performed 5 days to 30 minutes before percutaneous vertebroplasty and also at 30 minutes after the injection of bone cement. The difference between preprocedural and postprocedural data of Pao(2) was correlated with patients' age, number of treated vertebral bodies, presence of cement leakage, and presence of malignant neoplasm for each patient. RESULTS: Mean pre-Pao(2) and post-Pao(2) were 80.9 +/- 1.4 and 70.6 +/- 1.3 mm Hg (mean +/- SE) respectively (P = .0001). Using analysis of variance, there was a significant difference according to the number of vertebral bodies. There was a positive trend of decrease in Pao(2) according to the number of vertebral bodies during percutaneous vertebroplasty. Using multiple linear regression and after adjusting by preprocedural Pao(2) and other variables, the number of vertebral bodies was still highly significant. CONCLUSION: Pao(2) decreases during percutaneous vertebroplasty, and there is a correlation between the number of treated vertebral bodies and decrease in Pao(2).

Advanced Statistical Analyses to Reduce Inconsistency of Bond Strength Data.

This study was designed to clarify the interrelationship of factors that affect the value of microtensile bond strength (µTBS), focusing on nondestructive testing by which information of the specimens can be stored and quantified. µTBS test specimens were prepared from 10 noncarious human molars. Six factors of µTBS test specimens were evaluated: presence of voids at the interface, X-ray absorption coefficient of resin, X-ray absorption coefficient of dentin, length of dentin part, size of adhesion area, and individual differences of teeth. All specimens were observed nondestructively by optical coherence tomography and micro-computed tomography before µTBS testing. After µTBS testing, the effect of these factors on µTBS data was analyzed by the general linear model, linear mixed effects regression model, and nonlinear regression model with 95% confidence intervals. By the general linear model, a significant difference in individual differences of teeth was observed ( P < 0.001). A significantly positive correlation was shown between µTBS and length of dentin part ( P < 0.001); however, there was no significant nonlinearity ( P = 0.157). Moreover, a significantly negative correlation was observed between µTBS and size of adhesion area ( P = 0.001), with significant nonlinearity ( P = 0.014). No correlation was observed between µTBS and X-ray absorption coefficient of resin ( P = 0.147), and there was no significant nonlinearity ( P = 0.089). Additionally, a significantly positive correlation was observed between µTBS and X-ray absorption coefficient of dentin ( P = 0.022), with significant nonlinearity ( P = 0.036). A significant difference was also observed between the presence and absence of voids by linear mixed effects regression analysis. Our results showed correlations between various parameters of tooth specimens and µTBS data. To evaluate the performance of the adhesive more precisely, the effect of tooth variability and a method to reduce variation in bond strength values should also be considered.

Long-term visual outcomes of vitrectomy for cystoid macular edema due to nonischemic central retinal vein occlusion.

PURPOSE: To report the long-term surgical outcome of vitrectomy for cystoid macular edema due to nonischemic central retinal vein occlusion (CRVO). METHODS: A retrospective chart review of 25 consecutive eyes (25 patients) with cystoid macular edema due to nonischemic CRVO treated with vitrectomy was performed. All patients underwent a pars plana vitrectomy with the creation of a posterior vitreous detachment if still attached. Simultaneous phacoemulsification with intraocular lens implantation was also performed in phakic eyes. The main outcome measures were best-corrected visual acuity (BCVA) and changes in macular edema shown by contact-lens biomicroscopy. The mean follow-up time was 49 months (range, 16-108). RESULTS: The median BCVA before surgery was 0.31 and the median BCVA at last follow-up was 0.67. The BCVA at the last follow-up improved at least two Snellen lines in 17 (68%), remained unchanged in 4 (16%), and worsened in 4 (16%). The BCVA was 20/40 or better in 3 eyes (12%) preoperatively and in 18 eyes (72%) at the last follow-up. During the follow-up, four patients progressed to ischemic CRVO; one of them had neovascular glaucoma requiring surgical intervention. CONCLUSION: The data indicate that vitrectomy appears to be a possibly effective treatment in some eyes with cystoid macular edema associated with nonischemic CRVO.

Light compensation points in shade-grown seedlings of deciduous broadleaf tree species with different successional traits raised under elevated CO2.

We measured leaf photosynthetic traits in shade-grown seedlings of four tree species native to northern Japan, raised under an elevated CO2 condition, to investigate the effects of elevated CO2 on shade tolerance of deciduous broadleaf tree species with different successional traits. We considered Betula platyphylla var. japonica and Betula maximowicziana as pioneer species, Quercus mongolica var. crispula as a mid-successional species, and Acer mono as a climax species. The plants were grown under shade conditions (10% of full sunlight) in a CO2 -regulated phytotron. Light compensation points (LCPs) decreased in all tree species when grown under elevated CO2 (720 µmol·mol(-1) ), which were accompanied by higher apparent quantum yields but no photosynthetic down-regulation. LCPs in Q. mongolica and A. mono grown under elevated CO2 were lower than those in the two pioneer birch species. The LCP in Q. mongolica seedlings was not different from that of A. mono in each CO2 treatment. However, lower dark respiration rates were observed in A. mono than in Q. mongolica, suggesting higher shade tolerance in A. mono as a climax species in relation to carbon loss at night. Thus, elevated CO2 may have enhanced shade tolerance by lowering LCPs in all species, but the ranking of shade tolerance related to successional traits did not change among species under elevated CO2 , i.e. the highest shade tolerance was observed in the climax species (A. mono), followed by a gap-dependent species (Q. mongolica), while lower shade tolerance was observed in the pioneer species (B. platyphylla and B. maximowicziana).

Investigation on the interactions of peptides in the assembly of liposome and peptide by fluorescence.

The peptide-lipid and the peptide-peptide interactions of hydrophobic linear dipeptides containing tryptophan in liposome were investigated by fluorescence. The linear dipeptides were buried into the hydrophobic region of liposome to induce blue-shift of the fluorescence. With the addition of various anthracene derivatives to liposome, the energy transfer from tryptophan to anthryl group took place, which increased as the temperature decreased below the phase-transition temperature of the membrane. This phenomenon was explained in terms of the phase separation of the membrane, in which crystalline regions without the probes and the domains containing high concentrations of probes are intermixed. The energy-transfer efficiency was larger in the case of peptide acceptors than lipid acceptors. This suggests the presence of special interactions between donor peptide and acceptor peptide.

Structural basis of pathogen recognition by an integrated HMA domain in a plant NLR immune receptor.

Plants have evolved intracellular immune receptors to detect pathogen proteins known as effectors. How these immune receptors detect effectors remains poorly understood. Here we describe the structural basis for direct recognition of AVR-Pik, an effector from the rice blast pathogen, by the rice intracellular NLR immune receptor Pik. AVR-PikD binds a dimer of the Pikp-1 HMA integrated domain with nanomolar affinity. The crystal structure of the Pikp-HMA/AVR-PikD complex enabled design of mutations to alter protein interaction in yeast and in vitro, and perturb effector-mediated response both in a rice cultivar containing Pikp and upon expression of AVR-PikD and Pikp in the model plant Nicotiana benthamiana. These data reveal the molecular details of a recognition event, mediated by a novel integrated domain in an NLR, which initiates a plant immune response and resistance to rice blast disease. Such studies underpin novel opportunities for engineering disease resistance to plant pathogens in staple food crops.

Spatial memory disturbance after focal cerebral ischemia in rats.

We investigated the impairment of retention of spatial memory in rats with chronic focal cerebral ischemia, and examined the correlation between this impairment and pathological outcomes. A preoperative acquisition trial of the Morris water-maze task was performed twice a day for 14 successive days, and then the middle cerebral artery (MCA) was occluded. A retention trial was performed 8 weeks after MCA occlusion. Escape latency and swimming path length to the platform were significantly increased in MCA-occluded rats compared with those of sham-operated rats, and these deficits significantly correlated with massive shrinkage of the brain. Retention latency of a passive avoidance task, which was trained preoperatively, was also significantly shortened in MCA-occluded rats compared with that in sham-operated rats. These results suggest that chronic focal cerebral ischemia causes prolonged spatial memory disturbance in rats and is associated with pathological changes, and that this rat model may be useful for assessing not only anterograde but also retrograde amnesia caused by focal cerebral ischemia.

Oral-mucosal administration of IFN-alpha potentiates immune response in mice.

We studied the effects of oral-mucosal administration of murine interferon-alpha (Mu-IFN-alpha) on immune responses and infection with vaccinia virus (VV) in mice. When Mu-IFN-alpha was administered to sheep red blood cell (SRBC)-sensitized mice for 4 or 5 days, Mu-IFN-alpha significantly enhanced delayed-type hypersensitivity (DTH) and antibody production, with maximum enhancement of each at 1 IU/body. To investigate the antiviral effect of oral-mucosal Mu-IFN-alpha, mice were infected with VV, and Mu-IFN-alpha was administered for 15 days. Pocks were observed in the tail skin of infected mice, and Mu-IFN-alpha at doses of 1, 10, and 100 IU/body significantly suppressed pock formation. Also, VV-specific cytotoxic T cells (CTL) were observed in the spleen from the same mice at 7 days after infection, and Mu-IFN-alpha enhanced CTL activity at doses above 1 IU/body. These results suggest that the oral-mucosal Mu-IFN-alpha may have potentiating effects on cellular and humoral immune responses, which may contribute to its effects against VV.

Soluble thrombomodulin purified from human urine exhibits a potent anticoagulant effect in vitro and in vivo.

We examined the anticoagulant activity of two major molecules of soluble thrombomodulin purified from human urine. The apparent molecular weights of these urinary thrombomodulins (UTMs) were 72,000 and 79,000, respectively. Both UTMs showed more potent cofactor activity for protein C activation [specific activity > 5,000 thrombomodulin units (TMU)/mg] than human placental thrombomodulin (2,180 TMU/mg) and rabbit lung thrombomodulin (1,980 TMU/mg). The UTMs prolonged thrombin-induced fibrinogen clotting time (> 1 TMU /ml), APTT (> 5 TMU/ml), TT (> 5 TMU/ml) and PT (> 40 TMU/ ml) in a dose-dependent fashion. These effects appeared in the concentration range of soluble thrombomodulins present in human plasma and urine. In the rat DIC model induced by thromboplastin, administration of UTMs by infusion (300-3,000 TMU/kg) restored the hematological abnormalities derived from DIC in a dose-dependent fashion. These results demonstrate that UTMs exhibit potent anticoagulant and antithrombotic activities, and could play a physiologically important role in microcirculation.

Subretinal surgery for choroidal neovascularization in patients with high myopia.

OBJECTIVE: To analyze the visual outcome in patients undergoing surgical removal of subfoveal choroidal neovascularization (CNV) in eyes with high myopia. METHODS: We retrospectively reviewed the medical records of 48 consecutive patients with high myopia (> or =6 diopters [D]) who underwent vitrectomy with surgical removal of subfoveal CNV. The patient population consisted of 2 groups. Group 1 included 23 patients with findings only of myopic degeneration, and group 2 included 25 patients with presumed ocular histoplasmosis syndrome and myopia of 6 D or more. RESULTS: In group 1, the visual acuity improved by 2 or more Snellen lines in 9 eyes (39%), decreased in 8 eyes (35%), and remained unchanged in 6 (26%), with a mean follow-up of 24 months (range, 8-60 months). The preoperative visual acuity was 20/40 or better in only 1 eye (4%), but 8 (35%) achieved a final visual acuity of 20/40 or better. In group 2, the visual acuity improved in 16 eyes (64%), was stable in 4 (16%), and deteriorated in 5 (20%), with a mean follow-up of 18 months (range, 6-44 months). Only 3 eyes (12%) had a preoperative visual acuity of 20/40 or better, but 11 (44%) achieved a final visual acuity of 20/40 or better. Recurrence occurred in 13 (57%) of the 23 eyes in group 1 and in 9 (36%) of the 25 eyes in group 2. Univariate analysis demonstrated a significant relation between younger patient age (group 1) and absence of postoperative CNV recurrence (group 2) and an improvement of visual acuity (P<.01). CONCLUSIONS: Surgical removal of CNV may provide visual benefit in selected cases of subfoveal CNV associated with high myopia. The determination of whether surgical intervention is appropriate in these cases requires a prospective, randomized, clinical trial.

Visual outcome after surgical removal of choroidal neovascularization in pediatric patients.

OBJECTIVE: To assess the visual outcome after surgical removal of choroidal neovascularization (CNV) in pediatric patients. METHODS: A retrospective, noncomparative, consecutive case series of 17 eyes undergoing surgical removal of CNV of various causes in patients aged 18 years and younger. RESULTS: The cause of the CNV was presumed ocular histoplasmosis syndrome in 11 eyes, idiopathic in 3, and optic nerve coloboma, ocular toxoplasmosis, and trauma in 1 eye each. Two eyes had CNV within 100 microm of the center of the foveal avascular zone (juxtafoveal CNV) and 1 eye had peripapillary CNV, while 14 eyes had CNV beneath the geometric center of the foveal avascular zone (subfoveal CNV). In eyes with subfoveal CNV, median preoperative Snellen visual acuity was 20/200 (range, 20/80-3/200). With a median follow-up of 27 months (range, 6-45 months), median final visual acuity was 20/50 (range, 20/20-2/200); 10 (72%) had improvement of 2 or more Snellen lines after surgery, and 6 eyes (43%) had final visual acuity of 20/40 or better. In 3 eyes with juxtafoveal CNV or peripapillary CNV, all eyes had improvement of 4 or more Snellen lines. Postoperative recurrent CNV developed in 6 (35%) of 17 patients; 2 of the eyes underwent a second vitrectomy and 4 received laser treatment for the recurrences. CONCLUSIONS: Pediatric patients may have good recovery of vision after surgical removal of CNV, and the removal of these membranes may be a viable alternative to laser photocoagulation in pediatric patients.

Initial stages of posterior vitreous detachment in healthy eyes of older persons evaluated by optical coherence tomography.

OBJECTIVE: To promote understanding of the development of posterior vitreous detachment (PVD) in healthy eyes using optical coherence tomography (OCT). METHODS: We studied 209 eyes of 209 healthy volunteers (165 men and 44 women; mean age, 52.3 years [range, 31-74 years]). In addition to biomicroscopy and ophthalmoscopy, OCT was performed to obtain high-resolution cross-sectional images of the vitreoretinal interface in the posterior fundus. RESULTS: The condition of the posterior vitreoretinal interface was classified as 1 of 5 stages, according to biomicroscopic findings and OCT images relative to discrete linear signals indicating a detached posterior vitreous face: stage 0, no PVD (61 eyes [29.2%]); stage 1, incomplete perifoveal PVD in up to 3 quadrants (100 eyes [47.8%]); stage 2, incomplete perifoveal PVD in all quadrants, with residual attachment to the fovea and optic disc (26 eyes [12.4%]); stage 3, incomplete PVD over the posterior pole, with residual attachment to the optic disc (4 eyes [1.9%]); or stage 4, complete PVD identified with biomicroscopy, but not with OCT because of instrument limitations (18 eyes [8.6%]). Stage 1, 2, and 3 incomplete PVD without subjective symptoms was not recognizable on contact lens biomicroscopy. There was a significant age-related progression in the condition of the vitreoretinal interface from stage 0 to stage 4. The superior quadrant was usually the initial site of incomplete PVD. CONCLUSIONS: Optical coherence tomography demonstrates that healthy human eyes have incomplete or partial PVD beginning as early as the fourth decade of life. Age-related PVD occurs initially as a focal detachment in the perifovea of 1 quadrant, with persistent attachment to the fovea and optic nerve head, with a predilection for the superior quadrant. It extends its range slowly for years and eventually results in complete PVD, associated with release of vitreopapillary adhesion.

Fate alteration of neuroepithelial cells from neurogenesis to astrocytogenesis by bone morphogenetic proteins.

Bone morphogenetic proteins (BMPs), a class of cytokines belonging to the transforming growth factor-beta superfamily, have been shown to play a wide variety of roles during development including those in the central nervous system. We here report that BMP2, BMP4 and BMP7 have an equivalent potential to inhibit neurogenesis and concomitantly induce astrocytogenesis of mouse fetal neuroepithelial cells. We further show that these BMPs activate a promoter of the gene for negative helix-loop-helix (HLH) factor, Id1, which is known to inhibit the function of such neurogenic transcription factors as Mash1 and neurogenin. These results suggest that BMP2, BMP4 and BMP7 alternate the fate of neuroepithelial cells from neuronal type to astrocytic one via a common mechanism involving negative HLH factor.

A novel prolyl endopeptidase inhibitor, JTP-4819, with potential for treating Alzheimer's disease.

The pharmacological actions of JTP-4819, a new prolyl endopeptidase (PEP) inhibitor targeted for the treatment of Alzheimer's disease, are reviewed with respect to its effects on PEP activity, brain neurotransmitters, and memory-related behaviour in rats. JTP-4819 was shown to be a very potent and specific inhibitor of PEP. At nanomolar concentration, JTP-4819 inhibited the degradation of substance P, arginine-vasopressin, and thyrotropin-releasing hormone by PEP in supernatants of the rat cerebral cortex and hippocampus. Repeated administration of JTP-4819 reversed the aging-induced decrease in brain substance P-like and thyrotropin-releasing hormone-like immunoreactivity, suggesting that this drug may be able to improve the imbalance of peptidergic neuronal systems that develops with senescense by inhibiting PEP activity. JTP-4819 increased acetylcholine release from the frontal cortex and hippocampus, regions closely associated with memory, in both young and aged rats. In addition, it improved performance in several memory and learning-related tests (e.g., the Morris water maze task in aged or MCA-occluded rats and the passive avoidance test). This memory-enhancing effect of JTP-4819 may result from prevention of the metabolic degradation of brain neuropeptides by PEP as well as from the enhancement of acetylcholine release. Taken together, these unique and potent pharmacological actions of JTP-4819 suggest that it may have the potential to be used for treating Alzheimer's disease.

Interleukin-2 enhances the viability of primary cultured rat neocortical neurons.

We determined the neurotrophic activity of interleukin-2 (IL-2) on primary cultured neocortical neurons from embryonic rat brain. IL-2 clearly enhanced the viability of cultured neurons in a dose-dependent manner. The neurotrophic effect of IL-2 was completely neutralized by IL-2 antibody. Furthermore, expression of IL-2 receptor mRNA was more pronounced in neurons than in other cultured cells such as astroglia and microglia. These results strongly suggest that IL-2 plays certain roles in the central nervous system as a neurotrophic factor.