The extracellular-to-total body water ratio reflects improvement in the activities of daily living in patients who experienced acute stroke.

OBJECTIVES: To determine the relationship between bioelectrical impedance analysis (BIA) parameters, including the extracellular water-to-total body water ratio (ECW/TBW), and the activities of daily living (ADL) improvement, in patients who experienced acute stroke. MATERIALS AND METHODS: This retrospective cohort study included 307 patients (mean age, 72 years; 39 % female) who experienced acute stroke and were admitted to the stroke unit of the Nippon Medical School Hospital (Bunkyo-ku, Tokyo, Japan) between April 2021 and March 2022. The Functional Independence Measure (FIM) was assessed at initial rehabilitation and discharge, and FIM effectiveness was calculated as ADL improvement in the participating acute care hospitals. BIA markers included the skeletal muscle mass index (SMI), phase angle (PhA), and ECW/TBW. Multiple linear regression models were used to estimate the relationship between the FIM effectiveness and each BIA marker. RESULTS: The mean (±SD) FIM effectiveness was 0.45 ± 0.36. The proportions of low SMI (male, <7.0 kg/m2; female, <5.7 kg/m2) and low PhA (male <5.36 degrees, female <3.85 degrees), were 48.9 % and 43.3 %, respectively. In addition, the proportions of of low (<0.36), normal (0.36-0.40), and high (>0.4) ECW/TBW ratios were 1.3 %, 78.5 %, and 20.2 %, respectively. After adjustments for demographic and clinical variables, low PhA, low ECW/TBW, and high ECW/TBW were all significantly associated with FIM effectiveness (P < 0.05), with ß coefficients of -0.126, -0.089, and -0.117, respectively. CONCLUSIONS: Low and High ECW/TBW and low PhA levels were negatively correlated with improvements in ADL. The ECW/TBW ratio may be an additional indicator of rehabilitation trainability in patients who experience acute stroke.

Nanos3 of the frog Rana rugosa: Molecular cloning and characterization.

Nanos is expressed in the primordial germ cells (PGCs) and also the germ cells of a variety of organisms as diverse as Drosophila, medaka fish, Xenopus and mouse. In Nanos3-deficient mice, PGCs fail to incorporate into the gonad and the size of the testis and ovary is thereby dramatically reduced. To elucidate the role of Nanos in an amphibian species, we cloned Nanos3 cDNA from the testis of the R. rugosa frog. RT-PCR analysis showed strong expression of Nanos3 mRNA in the testis of adult R. rugosa frogs, but expression was not sexually dimorphic during gonadal differentiation. In Nanos3-knockdown tadpoles produced by the CRISPR/Cas9 system, the number of germ cells decreased dramatically in the gonads of both male and female tadpoles before sex determination and thereafter. This was confirmed by three dimensional imaging of wild-type and Nanos3 knockdown gonads using serial sections immunostained for Vasa, a marker specific to germ cells. Taken together, these results suggest that Nanos3 protein function is conserved between R. rugosa and mouse.

The cutoff values of functional independence measure scores for predicting discharge destination in the early stroke phase.

This study aimed to determine cutoff values of functional independence measure (FIM) scores to predict the discharge destinations of patients with acute stroke. The sample included 318 patients with acute stroke (mean age, 72.0 years; women, 39%). The discharge destination was categorized into three groups: home, postacute rehabilitation (hospital with convalescent rehabilitation wards), and postacute care (institution without convalescent rehabilitation wards). We assessed FIM after lifting bed restriction. Multinomial logistic regression analyses were used to estimate odds ratios (OR) and 95% confidence intervals (CI) of the FIM scores for predicting discharge destinations, with postacute rehabilitation as a reference. Cutoff values of motor and cognitive FIM scores for distinguishing home from postacute rehabilitation and postacute care from postacute rehabilitation were determined using receiver operating characteristic curves. The proportion of home, postacute rehabilitation, and postacute care were 34.6%, 41.8%, and 23.6%, respectively. After adjustments for clinical variables, the ORs (95% CIs) for motor and cognitive FIM scores for home versus postacute rehabilitation were 1.08 (1.04-1.11) and 1.05 (0.98-1.12). Furthermore, those for postacute care versus postacute rehabilitation were 1.01 (0.98-1.04) and 0.92 (0.87-0.98). The cutoff values of the motor and cognitive FIM scores for distinguishing home from postacute rehabilitation were 37.5 (sensitivity: 0.92; specificity: 0.64) and 23.5 (sensitivity: 0.78; specificity: 0.67). Furthermore, those for distinguishing postacute care from postacute rehabilitation were 15.5 (sensitivity, 0.81; specificity, 0.51) and 12.5 (sensitivity, 0.74; specificity, 0.64). The identified cutoff values may serve as early indicators for predicting discharge destinations from acute stroke care.

Urinary Amino Acid-Conjugated Acrolein and Taurine as New Biomarkers for Detection of Dementia.

BACKGROUND: Dementia, including Alzheimer's disease (AD), is one of the serious diseases at advanced age, and its early detection is important for maintaining quality of life (QOL). OBJECTIVE: In this study, we sought novel biomarkers for dementia in urine. METHODS: Samples of urine were collected from 57 control subjects without dementia, 62 mild cognitive impairment (MCI) patients, and 42 AD patients. Mini-Mental State Examination (MMSE) was evaluated when subjects were examined by medical doctors. Urinary amino acid (lysine)-conjugated acrolein (AC-Acro) was measured using N ɛ-(3-formyl-3, 4-dehydropiperidine) lysine (FDP-Lys) ELISA kit, and taurine content was measured using a taurine assay kit. Values were normalized by creatinine content which was measured with the colorimetric assay kit. RESULTS: We found that urinary amino acid (lysine)-conjugated acrolein (AC-Acro) and taurine negatively correlated with MMSE score and are significantly lower in dementia patients compared to the normal subjects. When AC-Acro and taurine were evaluated together with age using an artificial neural network model, median relative risk values for subjects with AD, subjects with mild cognitive impairment, and control subjects were 0.96, 0.53, and 0.06, respectively. CONCLUSION: Since urine is relatively easy to collect, our findings provide a novel biomarker for dementia without invasiveness.

Augmented glutathione synthesis decreases acrolein toxicity.

We have shown recently that acrolein is more strongly involved in cell damage than reactive oxygen species during brain infarction. Thus, we tried to isolate cells with reduced susceptibility to acrolein toxicity to clarify how acrolein is detoxified under cell culture conditions. The IC(50) of acrolein in mouse mammary carcinoma FM3A cells and in neuroblastoma Neuro2a cells was 2.6 and 4.2µM, respectively, but in acrolein toxicity-decreasing FM3A (FM3A-ATD) cells and Neuro2a (Neuro2a-ATD) cells, it was 7.6 and 8.4µM, respectively. In both FM3A-ATD and Neuro2a-ATD cells, the concentration of glutathione (GSH) was increased, so that detoxification occurred through acrolein conjugation with GSH. In FM3A-ATD cells, the level of a rate-limiting enzyme of GSH synthesis, γ-glutamylcysteine ligase catalytic unit (GCLC), was increased through the reactivation of one inactive allele of GCLC genes in FM3A cells. In Neuro2a-ATD cells, phosphorylation of transcription factors (c-Jun and NF-κB) necessary for expression of genes for GCLC and glutathione synthetase (GSHS) involved in GSH synthesis was stimulated, so that transcription of two genes increased in Neuro2a-ATD cells. Phosphorylation of JNK (c-Jun N-terminal kinase), which catalyzes phosphorylation of c-Jun and NF-κB p65, was also increased in Neuro2a-ATD cells, suggesting that activation of JNK kinase is responsible for the increase in GSH. These results support the idea that GSH plays important roles in detoxification of acrolein, because GSH is increased in both FM3A-ATD and Neuro2a-ATD cells.

Brain infarction correlates more closely with acrolein than with reactive oxygen species.

Although it is thought that the major factor responsible for cell damage is reactive oxygen species (ROS), our recent studies have shown that acrolein is more toxic than ROS. Thus, the relative importance of acrolein and ROS in cell damage during brain infarction was compared using photochemically induced thrombosis model mice. The levels of acrolein-conjugated albumin, and of 4-hydroxynonenal (HNE)-conjugated albumin and 8-OHdG were evaluated as indicators of damage produced by acrolein and ROS, respectively. The increase in acrolein-conjugated albumin was much greater than the increase in HNE-conjugated albumin or 8-OHdG, suggesting that acrolein is more strongly involved in cell damage than ROS during brain infarction. It was also shown that infarction led more readily to RNA damage than to DNA or phospholipid damage. As a consequence, polyamines were released from RNA, and acrolein was produced from polyamines, especially from spermine by spermine oxidase. Production of acrolein from spermine by spermine oxidase was clarified using spermine synthase-deficient Gy mice and transglutaminase 2-knockout mice, in which spermine content is negligible or spermidine/spermine N(1)-acetyltransferase activity is elevated.

Translational control of hippocampal synaptic plasticity and memory by the eIF2alpha kinase GCN2.

Studies on various forms of synaptic plasticity have shown a link between messenger RNA translation, learning and memory. Like memory, synaptic plasticity includes an early phase that depends on modification of pre-existing proteins, and a late phase that requires transcription and synthesis of new proteins. Activation of postsynaptic targets seems to trigger the transcription of plasticity-related genes. The new mRNAs are either translated in the soma or transported to synapses before translation. GCN2, a key protein kinase, regulates the initiation of translation. Here we report a unique feature of hippocampal slices from GCN2(-/-) mice: in CA1, a single 100-Hz train induces a strong and sustained long-term potentiation (late LTP or L-LTP), which is dependent on transcription and translation. In contrast, stimulation that elicits L-LTP in wild-type slices, such as four 100-Hz trains or forskolin, fails to evoke L-LTP in GCN2(-/-) slices. This aberrant synaptic plasticity is mirrored in the behaviour of GCN2(-/-) mice in the Morris water maze: after weak training, their spatial memory is enhanced, but it is impaired after more intense training. Activated GCN2 stimulates mRNA translation of ATF4, an antagonist of cyclic-AMP-response-element-binding protein (CREB). Thus, in the hippocampus of GCN2(-/-) mice, the expression of ATF4 is reduced and CREB activity is increased. Our study provides genetic, physiological, behavioural and molecular evidence that GCN2 regulates synaptic plasticity, as well as learning and memory, through modulation of the ATF4/CREB pathway.

Identification of acrolein-conjugated protein in plasma of patients with brain infarction.

It is known that the level of protein-conjugated acrolein in plasma is a good marker of chronic renal failure and brain infarction. Thus, studies were carried out to determine which kinds of plasma proteins are conjugated with acrolein. It was found that acrolein was mainly conjugated with albumin. Tandem mass spectrometry analysis demonstrated that Lys-557 and Lys-560, located at the surface of domain III of albumin, were the major sites conjugated with acrolein. This is the first report to identify the amino acid residues in a protein modified by acrolein in vivo. It was found that conjugation of acrolein with albumin contributed to a decrease in the toxicity of acrolein.

Development of an ELISA for Measurement of Urinary 3-Hydroxypropyl Mercapturic Acid (3-HPMA), the Marker of Stroke.

We previously observed an inverse correlation between stroke and urinary 3-hydroxypropyl mercapturic acid (3-HPMA), an acrolein-glutathione metabolite, through its measurement by liquid chromatography with tandem mass spectrometry (LC-MS/MS). However, the cost of equipment for LC-MS/MS and its maintenance fee is very expensive and a cost-efficient method is required. In this study, we have developed a sensitive enzyme-linked immunosorbent assay (ELISA) system to measure 3-HPMA using a chicken antibody recognizing 3-HPMA-conjugated chicken albumin as antigen. Linearity to measure 3-HPMA was obtained from 0 to 10 µM, indicating that this ELISA system is useful for measurement of urine 3-HPMA. It was confirmed that 3-HPMA in urine of stroke patients decreased significantly compared with that of control subjects using the ELISA system. Using the ELISA kit, it became possible to evaluate the risk of brain stroke by not only plasma but also by urine. These results confirm that shortage of glutathione to detoxify acrolein is one of the major causes of stroke incidence. Our method contributes to maintenance of quality of life (QOL) of the elderly.

Acrolein toxicity: Comparison with reactive oxygen species.

The toxicity of acrolein was compared with that of reactive oxygen species using a mouse mammary carcinoma FM3A cell culture system. Complete inhibition of cell growth was accomplished with 10 microM acrolein, 100 microM H(2)O(2), and 20 microM H(2)O(2) plus 1mM vitamin C, which produce ()OH, suggesting that toxicity of acrolein is more severe than H(2)O(2) and nearly equal to that of ()OH, when these compounds were added extracellularly. Acrolein toxicity was prevented by N-acetyl-l-cysteine and N-benzylhydroxylamine, and attenuated by putrescine and spermidine. Toxicity of H(2)O(2) was prevented by glutathione peroxidase plus N-acetyl-l-cysteine, pyruvate, catalase, and reduced by polyphenol, and toxicity of ()OH was prevented by glutathione peroxidase plus N-acetyl-l-cysteine, pyruvate, catalase and reduced by N-acetyl-l-cysteine. The results indicate that prevention of cell toxicity by N-acetyl-l-cysteine was more effective with acrolein than with ()OH. Protein and DNA synthesis was damaged primarily by acrolein and reactive oxygen species, respectively.

Iris pigment epithelial cell transplantation for degenerative retinal diseases.

The transplantation of different types of cells into the eye to treat retinal diseases has advanced in the past 20 years. One of the types of cells used for transplantation is the iris pigment epithelial (IPE) cell, because autologous IPE cells are easily obtained and their properties are similar to those of retinal pigment epithelial (RPE) cells and retinal cells. IPE cells are transplanted as; freshly isolated or cultured cells to replace defective or diseased RPE cells, genetically modified IPE cells for delivering target molecules to the retina or RPE, and retinal progenitor cells. IPE cells have also been transplanted for non-retinal disorders. The survival of the transplanted cells in the host is an important factor for the success of transplantation. Autologous IPE cells have been found in the transplanted subretinal space and were able to phagocytose rod outer segments even 6 months after transplantation. Allogeneic and xenogenic cells will not remain in the region longer than autologous cells. Allogenic cells transplanted into the subretinal space are rejected in humans. Thus, we have transplanted cultured autologous IPE cells in 56 patients with age-related macular degeneration. The long-term results (more than 2 years with a maximum of 8 years) showed that the visual acuity (VA) was significantly improved over the pre-transplantation VA, although a slight decrease of VA was observed 2 weeks after the transplantation. One patient showed a vasculitis-like lesion. IPE cells that were transduced with neurotrophic factors by plasmid or viral vectors have also been transplanted in animals. We have transduced several neurotrophic factor genes into IPE cells with a plasmid vector, adeno-associated virus, or adenovirus. Transplantation of these transduced IPE cells into the subretinal space rescued photoreceptor cells from several types of photoreceptor toxicities. In addition, transduction of a gene into the IPE cells suppressed the systemic dissemination of the viral genome. The neuroprotective effects of the IPE cells were different for the different types of neurotrophic factor, and some of the neurotrophic factors may enhance systemic immune reaction after transplantation. IPE cells have also been used as retinal progenital cells because they originate from the same cell lines that give rise to the neural retina and RPE cells. The transduction of the photoreceptor-related homeobox gene was reported to induce photoreceptor phenotypes in IPE cells. Furthermore, transplantations of IPE cells have been performed to treat central nervous system disorders. In this review, we summarize recent progress on IPE transplantation.

Expression of vasohibin, an antiangiogenic factor, in human choroidal neovascular membranes.

PURPOSE: To determine whether vasohibin, an antiangiogenic factor produced by vascular endothelial cells, is expressed in the choroidal neovascular (CNV) membranes obtained from human eyes with age-related macular degeneration (AMD) or polypoidal choroidal vasculopathy (PCV). DESIGN: Retrospective, interventional case series. METHODS: The medical charts of 21 eyes of 21 patients with AMD or PCV who underwent surgical removal of the CNV membrane were reviewed. The removed tissues were immunostained for von Willebrand Factor (vWF), vascular endothelial growth factor (VEGF), and vasohibin. The levels of the messenger ribonucleic acid of VEGF, VEGFR2, and vasohibin were determined by real-time reverse-transcriptase polymerase chain reaction (RT-PCR) from the CNV membranes excised from nine AMD and nine PCV patients. RESULTS: The patients were divided into three groups; four patients were placed in the most active group (Group H), 13 in the less active group (Group E), and four in the nonactive group (Group S). Immunohistochemistry showed that vasohibin, vWF, and VEGF were expressed in the vascular endothelial cells in the CNV membranes and in the polypoidal vessels. RT-PCR showed that there was a strong correlation between the level of expression of VEGFR2 and vasohibin (P = .0002). Eyes with a lower vasohibin-to-VEGF ratio tended to have larger subretinal hemorrhages or vitreous hemorrhages, whereas eyes with higher vasohibin-to-VEGF ratio had subretinal fibrosislike lesions. Statistical analysis of the vasohibin-to-VEGF ratio among the three groups was significant (P = .0209). CONCLUSIONS: Vasohibin is expressed in human CNV membranes. Our results indicate that the vasohibin-to-VEGF ratio may be related with the activity of the CNV.

Time dependent transition of the levels of protein-conjugated acrolein (PC-Acro), IL-6 and CRP in plasma during stroke.

OBJECTIVE: Measurement of plasma levels of protein-conjugated acrolein (PC-Acro) together with IL-6 and CRP can be used to identify silent brain infarction (SBI) with high sensitivity and specificity. The aim of this study was to determine how these biomarkers vary during stroke. METHODS: Levels of PC-Acro, IL-6 and CRP in plasma were measured on day 0, 2, 7 and 14 after the onset of ischemic or hemorrhagic stroke. RESULTS: After the onset of stroke, the level of PC-Acro in plasma was elevated corresponding to the size of stroke. It returned to near control levels by day 2, and remained similar through day 14. The degree of the decrease in PC-Acro on day 2 was greater when the size of brain infarction or hemorrhage was larger. An increase in IL-6 and CRP occurred after the increase in PC-Acro, and it was well correlated with the size of the injury following infarction or hemorrhage. The results suggest that acrolein becomes a trigger for the production of IL-6 and CRP, as previously observed in a mouse model of stroke and in cell culture systems. The increase in IL-6 and CRP was also correlated with poor outcome judging from mRS. CONCLUSION: The results indicate that the degree of the decrease in PC-Acro and the increase in IL-6 and CRP from day 0 to day 2 was correlated with the size of brain infarction, and the increase in IL-6 and CRP with poor outcome at discharge.

Correlation between brain damage, associated biomarkers, and medication in psychiatric inpatients: A cross-sectional study.

BACKGROUND: We clarified the correlation between brain damage, associated biomarkers and medication in psychiatric patients, because patients with schizophrenia have an increased risk of stroke. METHODS: The cross-sectional study was performed from January 2013 to December 2015. Study participants were 96 hospitalized patients (41 men and 55 women) in the Department of Psychiatry at Kohnodai Hospital, National Center for Global Health and Medicine, Ichikawa, Chiba, Japan. Patients were classified into schizophrenia (n=70) and mood disorders (n=26) by psychiatric diagnoses with DSM-IV-TR criteria. RESULTS: The incidence of brain damage [symptomatic and silent brain infarctions (SBIs) and white matter hyperintensity (WMH)] was correlated more with mood disorders than with schizophrenia. It has been previously shown that the concentrations of protein-conjugated acrolein (PC-Acro) and interleukin-6 (IL-6) increased in plasma of brain infarction patients together with C-reactive protein (CRP). The concentration of PC-Acro was significantly higher in patients with mood disorders than in those with schizophrenia. The concentration of IL-6 in both groups was nearly equal to that in the control group, but that of CRP in both groups, especially in mood disorders, was higher than that in the control group. Accordingly, the relative risk value for brain infarction was higher in patients with mood disorders than with schizophrenia. Medication with atypical antipsychotics reduced PC-Acro significantly in all psychiatric patients and reduced IL-6 in mood disorder patients. CONCLUSION: Measurement of 3 biomarkers (CRP, PC-Acro and IL-6) are probably useful for judgement of severity of brain damage and effectiveness of medication in psychiatric patients.

Polymorphisms in Complement Factor H and Hemicentin-1 genes in a Japanese population with dry-type age-related macular degeneration.

PURPOSE: To determine whether polymorphisms in the Complement Factor H (CFH) gene and the Hemicentin-1 gene at the ARMD1 locus are associated with dry age-related macular degeneration (AMD) in Japanese patients. DESIGN: Clinically relevant laboratory investigation. METHODS: Eighty unrelated Japanese patients with dry AMD and 196 Japanese control patients were studied. Two exons of the CFH gene and four exons of the Hemicentin-1 gene were amplified by polymerase chain reaction and sequenced directly. RESULTS: For the CFH gene, the frequency of the previously reported Tyr402His variant was not significantly higher in the AMD group than in the control group (P = .31). In the Hemicentin-1 gene, three sequence alterations (Asp5088Val, IVS99-13C/T, and His5245Gln) were detected, and the originally reported Gln5346Arg was not detected. CONCLUSION: The CFH gene and Hemicentin-1 genes do not appear to be involved in a statistically significant fraction of dry AMD cases in the Japanese population.

Hypothermia of 8 degrees C protects cultured retinal pigment epithelial cells and retinal ganglion cells against trypan blue toxicity.

PURPOSE: To determine whether hypothermia of 8 degrees C can protect cultured human retinal pigment epithelial (ARPE-19) cells and rat retinal ganglion cells (RGC-5) against trypan blue (TB) toxicity. DESIGN: Laboratory investigation. METHODS: ARPE-19 cells and RGC-5 were exposed to balanced salt solution as controls, and 0.05% and 0.5% TB at 37 degrees C, and at 8 degrees C for one minute. The percentage of surviving cells was determined by the resazurin test. RESULTS: TB induced a statistically significant decrease in the percentage of ARPE-19 cells surviving at 0.5% TB at 37 degrees C (P < .01). Conversely, TB induced a statistically significant decrease in the percentage of RGC-5 surviving at all conditions except for 0.05% TB at 8 degrees C (0.05% 37 degrees C; P < .05, 0.5% 37 degrees C and 8 degrees C; P < .01). CONCLUSIONS: These results indicate that reducing the temperature to 8 degrees C has a protective effect against the TB toxicity for ARPE-19 cells and RGC-5 in culture.

Evaluation of dementia by acrolein, amyloid-ß and creatinine.

Plasma, urine and cerebrospinal fluid (CSF) were examined for biochemical markers of dementia. Protein-conjugated acrolein (PC-Acro) and the amyloid-ß (Aß)40/42 ratio in plasma can be used to detect mild cognitive impairment (MCI) and Alzheimer's disease (AD). In plasma, PC-Acro and the Aß40/42 ratio in MCI and AD were significantly higher relative to non-demented subjects. Furthermore, urine acrolein metabolite, 3-hydroxypropyl mercapturic acid (3-HPMA)/creatinine (Cre) and amino acid-conjugated acrolein (AC-Acro)/Cre in AD were significantly lower than MCI. It was also shown that reduced urine 3-HPMA/Cre correlated with increased plasma Aß40/42 ratio in dementia. The Aß40/PC-Acro ratio in CSF, together with Aß40 and Aß40/42 ratio, was lower in AD than MCI. Increased plasma PC-Acro and Aß40/42 ratio and decreased urine 3-HPMA/Cre correlated with cognitive ability (MMSE). These results indicate that the measurements of acrolein derivatives together with Aß and Cre in biologic fluids is useful to estimate severity of dementia.

Distinguishing mild cognitive impairment from Alzheimer's disease with acrolein metabolites and creatinine in urine.

BACKGROUND: We previously reported that the level of urinary 3-hydroxypropyl mercapturic acid (3-HPMA)/creatinine (Cre) was reduced following stroke. The aim of this study was to determine whether the level of 3-HPMA/Cre in urine was reduced in subjects with dementia. METHODS: The level of 3-HPMA was measured by LC-MS/MS, and that of amino acid conjugated acrolein (AC-Acro) was by ELISA. The study included 128 elderly subjects divided into 74 non-demented (control), 22 mild cognitive impairment (MCI) and 32 Alzheimer's disease (AD) subjects. RESULTS: The urinary 3-HPMA/Cre and AC-Acro/Cre in MCI plus AD subjects were significantly lower than those in control subjects. In addition, urinary Cre in AD subjects was significantly higher than that in MCI subjects, and 3-HPMA/Cre and AC-Acro/Cre in AD subjects were significantly lower than that in MCI subjects. Among these three markers, the lower 3-HPMA/Cre ratio was most strongly correlated with the decline of MMSE (Mini-Mental State Examination) and the increase in CDRsob (Clinical Dementia Rating Scale Sum of Boxes Scores). Furthermore, reduction in 3-HPMA/Cre in urine was well correlated with increase in Aß40/42 in plasma in demented subjects. CONCLUSION: The results indicate that 3-HPMA/Cre in urine is the most reliable biochemical marker to distinguish AD subjects from MCI subjects among three markers.

Clinical features of bilateral acute idiopathic maculopathy.

PURPOSE: To describe the clinical course of bilateral acute idiopathic maculopathy (BAIM), and to analyze its pathophysiology. CASE: A 33-year-old Japanese woman presented with a sudden, severe, bilateral visual disturbance following a flu-like illness. She was examined by fluorescein angiography (FA), indocyanine green angiography (IA), scanning laser ophthalmoscopy (SLO), optical coherence tomography (OCT), and multifocal electroretinography (mfERG). OBSERVATIONS: A diagnosis of BAIM was made in this patient based on typical ophthalmoscopic features, which included a pathognomonic yellowish-white foveal lesion. FA demonstrated a breakdown of the outer blood-retinal barrier, with the size and location corresponding to the white lesion, and IA disclosed a choroidal circulatory disturbance. SLO demonstrated that the deep retinal and choroidal layers were disorganized, and OCT showed retinal edema. Electrophysiological dysfunction was detected by mfERGs. After steroid therapy, the patient's visual acuity recovered to normal. The pooling of fluorescein dye and the OCT-determined retinal edema were resolved. However, the physiological dysfunction detected by mfERGs remained. CONCLUSIONS: We conclude that the major abnormality in BAIM is an alteration of the retinal pigment epithelium causing severe edema.

Distinction between mild cognitive impairment and Alzheimer's disease by CSF amyloid ß40 and ß42, and protein-conjugated acrolein.

BACKGROUND: We found previously that the amyloid ß40/42 (Aß40/42) ratio and the level of protein-conjugated acrolein (PC-Acro) in plasma were increased in mild cognitive impairment (MCI) and Alzheimer's disease (AD) subjects. We determined whether MCI and AD subjects can be differentiated based on the levels of Aß40, Aß42, and PC-Acro in cerebrospinal fluid (CSF). METHODS: Aß40, Aß42, PC-Acro, Tau and phosphorylated Tau in CSF were measured by ELISA. RESULTS: Median values of Aß40, Aß40/PC-Acro and Aß40/42 in CSF were significantly lower in 54 AD subjects than those in 40 MCI subjects. Severity of VOI (volume of interest) atrophy was most intensely correlated with the decrease in Aß40/PC-Acro and then that in Aß40 and Aß42/PC-Acro. MMSE was most intensely correlated with the decrease in Aß42 and Aß40, and then that in Aß42/PC-Acro and Aß40/PC-Acro. CONCLUSION: A decrease in Aß40/PC-Acro in CSF is well correlated with brain damage, and a decrease in Aß42 and Aß40 is well correlated with cognitive ability. Measurement of PC-Acro together with Aß40 and Aß42 provides a more precise evaluation of severity of AD subjects.