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Background: Cerebral microbleeds (CMBs) detected on susceptibility-weighted imaging (SWI) are associated with cerebral small vessel disease. Chronic kidney disease and microalbuminuria have been associated with the presence of CMBs in stroke patients. Urinary immunoglobulin G (IgG) is measured to document glomerular injury; however, the relationship between urinary IgG and CMBs is unknown. Methods: We retrospectively enrolled consecutive patients who had been admitted with transient ischemic attack (TIA) or ischemic stroke and identified those who had undergone SWI and a spot urine test. The location of CMBs was classified on magnetic resonance imaging as strictly lobar, deep/infratentorial (D/I), or mixed areas. We analyzed the association between urinary IgG and the presence and location of CMBs. Results: We included 298 patients (86 female, median age 70 years, median eGFR 65.8 mL/min/1.73 m2). Positive urinary IgG and CMB results were found in 58 (19%) and 160 patients (54%), respectively. Urinary IgG positivity was significantly associated with CMBs compared with non-CMBs (28% vs. 9%, p < 0.001), and with D/I or mixed CMBs compared with non-D/I or mixed CMBs (34% vs. 10%, p < 0.001). Multivariate analysis revealed that urinary IgG and hypertension positivity were strongly associated with D/I or mixed CMBs (OR 3.479, 95% CI: 1.776–6.818, p < 0.001; OR 3.415, 95% CI: 1.863–6.258, p < 0.001). Conclusions: Urinary IgG was associated with the prevalence of D/I or mixed location CMBs in TIA or ischemic stroke patients. Our findings provide new insights into the association between urinary IgG and the distribution of CMBs.

Advanced glycation end products (AGEs) are suggested to play a potential role in the progression of Parkinson's disease (PD). The association between urinary levels of pentosidine, one of the best-characterized AGEs, and clinical conditions such as motor severity and cognition were investigated in patients with PD. Data on the clinical characteristics and urinary levels of pentosidine for 44 drug-naïve patients aged 60 years or older with PD were collected. The association between urinary pentosidine levels and severity of motor symptoms and cognition was analyzed using the Montreal Cognitive Assessment Scale (MoCA). Urinary pentosidine values increased with age (R

Striatal dopamine depletion is associated with not only motor symptom but also non-motor symptoms in patients with Parkinson’s disease (PD). The purpose is to elucidate the relation between heart rate variability (HRV) and dopaminergic depletion in specific striatal subregions. The subjects were 84 patients with newly diagnosed untreated PD. All patients underwent striatal 123I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (123I-FP-CIT) dopamine transporter single-photon emission computed tomography (DAT-SPECT). DaTQUANT software (GE Healthcare) was used as a semi-quantitative tool to analyze DAT-SPECT data. Association of HRV with dopaminergic depletion in specific striatal subregions was examined. HRV was related to dopamine depletion in the caudate and anterior putamen, especially the left side, after controlling for age, hemoglobin A1c level, disease duration, and motor severity on multiple regression analysis (left caudate; β = 0.269, p = 0.030, left anterior putamen; β = 0.315, p = 0.012). HRV was closely related to striatal dopamine depletion, especially in the left associative striatum, in patients with PD.

Monotherapy with monoamine oxidase B (MAO-B) inhibitors enhances the level of endogenous dopamine in treatment for Parkinson's disease (PD) and provides some benefits. Certain neuropsychiatric functions are also regulated by central dopaminergic activity.To investigate the relationship of the efficacy of monotherapy with MAO-B inhibitors on motor symptoms in PD with baseline cognitive function.Outcomes were examined for 27 consecutive drug-naïve PD patients who received initial treatment with a MAO-B inhibitor (selegiline: 11, rasagiline: 16). Selegiline was titrated to an optimal dose. The dose of rasagiline was fixed at 1 mg/day. Motor symptoms were assessed using the Movement Disorder Society-Unified Parkinson's Disease Rating Scale part III before treatment and after the efficacy reached a plateau within 19 weeks after drug initiation, and the % improvement in motor symptoms was calculated. Pre-treatment cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) and Frontal Assessment Battery (FAB). Correlations of % improvement in motor symptoms and baseline cognitive assessments were examined using Spearman correlation coefficients and multiple regression analysis.In all patients, the mean % improvement in motor symptoms was 46.5% (range 0-83.3%). Spearman correlation coefficients showed the % improvement in motor symptoms was correlated with FAB (r = 0.631, p 0.001). In multiple regression analysis with patient background factors as independent variables, only FAB was associated with improvement in motor symptoms in the MAO-B group.Better FAB scores predict a significant improvement in motor symptoms with treatment with MAO-B inhibitors, suggesting high activity of endogenous dopamine.

Some patients with Parkinson’s disease (PD) present with pareidolia, an illusion of a meaningless stimulus as a familiar object known to the observer. Since the striatum is associated with processing of visual information, we investigated correlations of pareidolia with motor symptoms and striatal dopaminergic function. A noise pareidolia test, assessment of motor symptoms using MDS-UPDRS and 123I-Ioflupane SPECT were performed in 58 drug-naive PD patients. A number of images in which a participant noticed an illusory face (number of illusory responses) were compared with motor assessment scores and uptake of 123I-ioflupane in the striatum. Of the 58 participants, 22 had at least one illusory response. Mean scores for MDS-UPDRS part III (p

Although high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) in chronic intracerebral hemorrhage (ICH) is beneficial, it has been poorly investigated in rTMS for acute ICH. Our aim is to investigate the effects and safety of rTMS in acute spontaneous ICH.We prospectively performed HF-rTMS on consecutive patients with ICH within 24 h from onset between April 2019 and August 2021. The inclusion criterion was (1) persistent paralysis, with an NIHSS scale of 1 or higher for at least 3 days after onset. The exclusion criteria were (1) cortical, subcortical, and cerebellar ICH, (2) disturbance of consciousness, and (3) over 80 years of age. For the purpose of comparison, we used a conventional rehabilitation group whose patients met the same criteria between April 2016 and March 2019. We evaluated incidence of epilepsy and exacerbation of the NIHSS score in the rTMS group. We also compared the two groups regarding clinical background and outcome.Enrolled in the study were a total of 44 patients. Of the patients, 22 (50%) were in the rTMS group. The median (IQR) time from onset to the start of rTMS was 9 (6-12) days. There were no cases of epilepsy or exacerbation of NIHSS after the start of rTMS. Favorable outcome (modified Rankin Scale score of between 0 and 2) at 3 months was frequently observed in the rTMS group (73% vs 27%, p = 0.006). HF-rTMS was independently associated with favorable outcome at 3 months (OR = 11.5, 95% CI = 2.194-60.447, p = 0.004).HF-rTMS may be safe and effective in acute ICH patients.

Introduction There is considerable intra- and inter-individual variability in the pharmacokinetics (PK) of levodopa after oral administration. Inter-individual variability in levodopa PK has also been demonstrated in fasting single-dose studies. We examined the factors that affect levodopa PK in patients with Parkinson's disease (PD) and quantified the intensity of their respective effects. Methods We studied 220 patients who underwent PK assessment after administration of 1 tablet of levodopa/DOPA decarboxylase inhibitor (DCI) combination, which contained 10 mg carbidopa/100 mg levodopa or 25 mg benserazide/100 mg levodopa. PK was evaluated using non-compartmental analysis. Results In total, 220 PD patients (including 112 men) were studied. The mean age (±standard deviation) and mean disease duration was 68.1 ± 8.9 and 7.7 ± 5.8 years, respectively. The Cmax of levodopa was 9.0 ± 4.0 ng/mL, Tmax was 41.4 ± 40.2 min, and area under the blood concentration–time curve up to 4 h (AUC4hr) was 12.3 ± 3.7 ng/mL*4hr. Factors affecting AUC4hr were analyzed using multiple linear regression models. Age (1.1 ± 0.23 per +10 years, p = 3.1E-8), sex (2.2 ± 0.5 for female, p = 1.9E-5), DCI (1.4 ± 0.4 for benserazide, p = 0.0028), and body weight (−0.77 ± 0.22 per +10 kg, p = 5.4E-4) were significantly related to AUC4hr, while disease duration, dyskinesia status, and eGFR were not related to AUC4hr and Cmax. Conclusion Female, aging, difference formulations of DCI, or lower body weight independently contributes to increased AUC4hr of levodopa in Japanese patients with PD in this study.

Objective The presence of deep venous thrombosis (DVT) in a cryptogenic stroke (CS) patient with a right-to-left shunt (RLS) may lead to the development of paradoxical embolism. The aim of the present was to investigate the prevalence of DVT and pulmonary embolism (PE) in CS patients and the clinical features of CS in relation to DVT location and the presence of PE. Methods The medical records of 903 patients with cerebral infarction were retrospectively reviewed. For patients with a diagnosis of CS, contrast saline transcranial color-coded sonography was performed to identify an RLS. DVT and PE were assessed by duplex ultrasonography and/or contrast-enhanced computed tomography. Proximal DVT (P-DVT) was defined as DVT in the popliteal, femoral, or iliac veins, and distal DVT (D-DVT) was defined as DVT at other locations. The patients were divided into three groups: CS with P-DVT and/or PE (P-DVT/PE) group; CS with D-DVT (D-DVT) group; and CS without DVT (no DVT) group. Results Seventy-two (37%) of 194 patients with CS had an RLS. The median time to first DVT examination from stroke onset was three days. Twenty-nine percent of CS patients with an RLS had DVT. The P-DVT/PE group comprised 8.3% of the CS patients with an RLS and included a larger number of patients with multi-territory infarction than the D-DVT group. The D-DVT and P-DVT/PE groups tended to be female and older, while the P-DVT/PE group tended to have pre-stroke disability. Conclusion CS patients, especially those with multi-territory lesions, should be immediately examined for DVT and PE.

Parkinson's disease (PD) is a neurodegenerative disease manifesting with motor and non-motor symptoms. Current treatment mainly relies on medication as a symptomatic therapy modulating neurotransmitters. Dopamine replacement therapy has been established, and levodopa is the gold standard for treatment of PD. However, the emergence of motor complications, such as a wearing-off phenomenon, is a clinical problem. Both primary symptoms and motor complications have been targets for the development of treatments for PD. Recent progression in the management of motor complications is supported by newly developed agents and advances in device and formulation technology to deliver drugs continuously. Elucidation of the pathophysiology of PD and the development of disease-modifying therapy that affects the underlying fundamental pathophysiology of the disease are also progressing. In this review, we introduce current knowledge on developments concerning medications for patients with PD.

Striatal dopamine depletion is associated with not only motor symptom but also non-motor symptoms in patients with Parkinson's disease (PD). The purpose is to elucidate the relation between heart rate variability (HRV) and dopaminergic depletion in specific striatal subregions. The subjects were 84 patients with newly diagnosed untreated PD. All patients underwent striatal

Background: Orthostatic hypotension (OH) at an early stage of Parkinson’s disease (PD) predicts poor prognosis, which may suggest degeneration of dopaminergic neurons affects sympathetic function, causing OH. Objective: We tested the hypothesis that striatal dopaminergic depletion is associated with OH in PD. Methods: Out of 99 patients with newly diagnosed untreated PD, 81 patients were enrolled according to our selection criteria. All patients underwent head-up tilt-table testing and striatal 123I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (123I-FP-CIT) dopamine transporter single photon emission computed tomography (DAT-SPECT). DaTQUANT software (GE Healthcare) was used as a semi-quantitative tool to analyze DAT-SPECT data. The association between hemodynamic changes and 123I-FP-CIT uptake was examined. Results: 123I-FP-CIT uptake in the putamen, especially the anterior part and left side, was related not only to motor severity but also to OH. Change in systolic blood pressure correlated negatively with 123I-FP-CIT uptake in bilateral anterior putamen (left: p

Objectives To investigate the differences in clinical backgrounds, especially weekly variations of stroke occurrence, between hyper-acute ischemic stroke patients with and without regular employment (RE), as well as the impact of RE on outcome. Materials and methods Symptomatic ischemic stroke patients with ≤4.5 h from onset to door were enrolled. First, we divided patients into the RE and non-RE group to analyze differences in clinical characteristics, especially relation between weekly variations of stroke occurrence and RE. Second, we divided the same patients into those with and without favorable outcomes (modified Rankin Scale score of 0 to 2 at 3 months from stroke onset) to analyze the impact of RE on outcomes. Results We screened 1,249 consecutive symptomatic ischemic stroke patients and included 377 patients (284 [75%] males; median age, 67 years). Of these patients, 248 (66%) were included in RE group. First, RE was independently associated with occurrence of stroke on Monday in reference to Sunday or a public holiday (OR 2.562, 95% CI 1.004-6.535, p = 0.049). Second, RE (OR 2.888 95% CI 1.378-6.050, p = 0.005) was a factor independently associated with a favorable outcome. Conclusions Patients with RE were more likely to have a hyper-acute ischemic stroke on Monday in reference to Sunday or a public holiday. However, RE before stroke onset appears to have a positive impact on outcome.

OBJECTIVES Minor hallucinations (MHs), including sense of presence, passage hallucinations, and visual illusions, have been reported in Parkinson's disease (PD). Here, we investigated the prevalence and associated risk factors for MHs according to appearance time. METHODS Data on the clinical characteristics and the appearance time of MHs for 100 PD patients were collected using a questionnaire and analyzed. MHs were classified into two groups according to the time when MHs appeared: MHs appearing while awake during the daytime (dMHs) and MHs appearing at arousal from sleep during the night or early morning (aMHs). RESULTS Thirty-eight patients (38%) experienced MHs. dMHs and aMHs were present in 21 (21%) and 28 patients (28%), respectively. Compared to patients without MHs, patients with dMHs had more severe motor symptoms, longer disease duration, higher levodopa equivalent daily dose (LEDD), and higher rates of cognitive impairment and visual hallucinations during the daytime, whereas patients with aMHs had a higher rate of rapid eye movement sleep behavior disorder (RBD), longer disease duration, higher LEDD, and higher dopamine agonist dosage. Logistic regression analysis showed that cognitive impairment was significantly associated with dMHs (odds ratio (OR) 7.292, p = .001), and that RBD (OR 8.306, p

Delayed orthostatic hypotension (DOH), a fall in blood pressure after a 3-min cutoff, is clinically meaningful. The aim of this study was to elucidate the clinical and neuroendocrinological characteristics of DOH in patients with Parkinson’s disease (PD). A total of 132 patients with newly diagnosed PD were enrolled. Baseline clinical characteristics, including olfactory function, and changes in norepinephrine (NE) and vasopressin (ADH) concentrations during the head-up tilt test (HUT), were examined. Fifty-five patients (42%) had classical orthostatic hypotension (COH), and 19 patients (14%) had DOH. Patients with COH and DOH tended to have more severe hyposmia than patients without OH. A multivariate linear regression model showed that hyposmia was associated with DOH and COH. The increase of heart rate against the fall in blood pressure was significantly lower in patients with COH and DOH than those without OH. The NE levels at supine rest and after upright tilting were lower in the COH group than in the PD without OH and DOH groups. The levels of ADH were higher in the DOH group than in the COH group at supine rest and higher than in the PD without OH group after upright tilting. There was no significant difference in the cardiac 123I-MIBG scintigraphy between the COH and DOH groups. Compared with patients without OH, patients with DOH had severe hyposmia. Relatively preserved peripheral sympathetic nervous system function in patients with DOH suggests that DOH might be an early and milder form of OH in PD.

The level of α-synuclein, a component of Lewy bodies, in cerebrospinal fluid (CSF) in Parkinson's disease (PD) has attracted recent attention. Most meta-analyses conclude that CSF levels of α-synuclein are decreased in PD. Patients with PD present with cognitive impairment, including frontal/executive dysfunction in the early phase and later emergence of visuospatial and mnemonic deficits. To examine whether CSF α-synuclein levels reflect the activities of various cognitive domains, we reviewed reports examining the association of these levels with cognitive performance in each domain in PD. Among 13 cross-sectional studies, five showed that a lower CSF α-synuclein level was associated with worse cognitive function. In four of these five reports, frontal/executive function showed this association, suggesting a link of the pathophysiology with Lewy bodies. In three other reports, a higher CSF α-synuclein level was associated with temporal-parieto-occipital cognitive deterioration such as memory. In the other five reports, the CSF α-synuclein level did not correlate with cognitive performance for any domain. In four longitudinal studies, a higher baseline CSF α-synuclein level was associated with a worse cognitive outcome, including cognitive processing speed, visuospatial function and memory in two, but not with any cognitive outcome in the other two. The different associations may reflect the heterogeneous pathophysiology in PD, including different pathogenic proteins, neurotransmitters. Thus, more studies of the association between cognitive domains and CSF levels of pathogenic proteins are warranted.

In patients with Parkinson's disease (PD), pulsatile dopaminergic stimulation may be a primary cause of levodopa-induced dyskinesia (LID). We aimed to investigate the correlation between levodopa pharmacokinetics (PK) and LID in PD.We retrospectively reviewed the consecutive series of 255 PD patients without LID who underwent PK assessments with 100 mg levodopa. The type of peripheral decarboxylase inhibitor used in the PK assessments was determined by the usual prescription of the formulations of levodopa (10 mg carbidopa [n = 185] and 25 mg benserazide [n = 70]).During a median follow-up of 32 months (IQR, 16-49 months), 73 patients (29%) developed LID. Compared with patients who did not develop LID (PD-LID-), those who developed LID (PD-LID+) were younger (p = 0.003) and had significantly higher maximum levodopa concentration (Cmax) (p = 0.002) and area under the curve (p 0.001), LEDD (p 0.001), and improvement of motor symptoms (p = 0.009). In the multivariate Cox proportional hazards models, Cmax and AUC were associated with incident LID (Hazard Ratio [HR] 1.11, 95% confidence interval [CI] 1.03-1.19 and HR 1.13, 95% CI 1.03-1.24, respectively). In addition, younger age, benserazide use, LEDD, and MAOBI use were associated with incident LID.High levodopa plasma concentration after oral administration was associated with incident LID in patients with PD.

Background and Purpose: We aimed to investigate the differences in weekly variations of stroke occurrence between hyper-acute ischemic stroke patients with and without regular employments (RE), and the impact of RE on outcome. Methods: Consecutive symptomatic ischemic stroke patients with < 4.5 h from onset to door between October 2012 and May 2018 were enrolled. All the situations of employment on admission were obtained from interviews with the participant or substitute guardians. First, we divided the patients into with and without RE to evaluate the differences in weekly variations of stroke occurrence. Second, we divided the same patients into with and without favorable outcome (mRS score of 0 to 2 at 3 months from the onset) to evaluate the impact of RE on outcome. Results: We screened 1,249 consecutive symptomatic ischemic stroke patients, including 385 patients (292 (76%) male, median age 67 years) with hyper-acute ischemic stroke. Of all, 251 patients (65%) were included in RE group. In the multivariate analysis, patients with RE were more likely to develop strokes on Monday compared to that on Sunday and public holiday (OR 2.841, 95% CI 1.145-7,049, p = 0.024, Figure A). In the multivariate analysis, the factors associated with favorable outcome were low NIHSS score on admission (OR 0.909, 95% CI 0.857-0.964, p = 0.001), not receiving endovascular therapy (OR 0.175 95% CI 0.069-0.444, p p = 0.039, Figure B). Conclusions: There were dramatic differences in weekly variations of hyper-acute ischemic stroke occurrence between patients with and without RE. Monday seems to be “a black day” for ischemic stroke patients with RE. RE had a positive impact on outcome in hyper-acute ischemic stroke.

An 86-year-old woman presented with generalized chorea in the face and extremities, which gradually progressed for two weeks. Cranial CT revealed a chronic subdural hematoma (CSDH) that covered the left parietal lobe. Discontinuation of amantadine did not improve the chorea. The hematoma was evacuated and the chorea completely subsided in a week. The pathogenesis leading to chorea in CSDH remains unclear. A unilateral hematoma presenting with generalized chorea similar to the present patient and two others with unilateral CSDH causing ipsilateral hemichorea have been reported. The rarity of these movement disorders due to CSDH indicates that these patients had a preclinical dysfunction within neuronal networks interconnecting basal ganglia the cerebral cortex. Our findings confirmed that CSDH could cause chorea, and further neuroimaging to evaluate cerebrovascular disease, taking a detailed family history and obtaining information about current medications might reveal factors likely to precipitate the development of chorea.

There is considerable intra- and inter-individual variability in the pharmacokinetics (PK) of levodopa after oral administration. Inter-individual variability in levodopa PK has also been demonstrated in fasting single-dose studies. We examined the factors that affect levodopa PK in patients with Parkinson's disease (PD) and quantified the intensity of their respective effects.We studied 220 patients who underwent PK assessment after administration of 1 tablet of levodopa/DOPA decarboxylase inhibitor (DCI) combination, which contained 10 mg carbidopa/100 mg levodopa or 25 mg benserazide/100 mg levodopa. PK was evaluated using non-compartmental analysis.In total, 220 PD patients (including 112 men) were studied. The mean age (±standard deviation) and mean disease duration was 68.1 ± 8.9 and 7.7 ± 5.8 years, respectively. The Cmax of levodopa was 9.0 ± 4.0 ng/mL, Tmax was 41.4 ± 40.2 min, and area under the blood concentration-time curve up to 4 h (AUCFemale, aging, difference formulations of DCI, or lower body weight independently contributes to increased AUC

Sympathetic nervous denervation may be associated with the development of anemia. We aimed to investigate the association between sympathetic nervous denervation and hemoglobin levels in patients with Parkinson’s disease (PD). As indices of sympathetic nervous denervation, we investigated resting norepinephrine levels, increased norepinephrine levels after tilt-up, cardiac uptake of 123I-metaiodobenzylguanidine, supine blood pressure, and the degree of orthostatic hypotension in 132 patients with de novo PD. Older age, female sex, severe motor dysfunction, and lower body mass index were associated with decreased hemoglobin levels. After adjustment for these covariables, resting norepinephrine levels were negatively associated with hemoglobin levels. Hemoglobin levels were not associated with cardiac sympathetic denervation or orthostatic intolerance. Hemoglobin levels in PD seem to be closely related to noradrenergic nervous activity and nigrostriatal dopaminergic degeneration. In contrast to expectations, decreased hemoglobin levels were associated with increased whole-body sympathetic nervous activity in PD.

Parkinson's disease (PD) patients can present with cognitive impairment, such as deficits in attention and memory processes, visual perception, executive function and social cognition. These dysfunctions negatively affect the activities of daily living and outcome of patients. Some of the risk factors, pathological background and etiology of cognitive dysfunction in PD with dementia (PDD) have been determined. Treatments for such dysfunctions are attracting much attention. Some medications, such as donepezil, rivastigmine, and memantine, have shown to improve motor and/or cognitive functions. Cognitive impairment and motor symptoms in PD can be treated concurrently. Therefore, the correlation between motor and cognitive function should be considered when treating PD.

The intensity and frequency of harmful algal blooms (HABs) have increased, posing a threat to human seafood resources due to massive kills of cultured fish and toxin contamination of bivalves. In recent years, bacteria that inhibit the growth of HAB species were found to be densely populated on the biofilms of some macroalgal species, indicating the possible biological control of HABs by the artificial introduction of macroalgal beds. In this study, an artificially created Ulva pertusa bed using mobile floating cages and a natural macroalgal bed were studied to elucidate the distribution of algal growth-limiting bacteria (GLB). The density of GLB affecting fish-killing raphidophyte Chattonella antiqua, and two harmful dinoflagellates, were detected between 106 and 107 CFU g&minus, 1 wet weight on the biofilm of artificially introduced U. pertusa and 10 to 102 CFU mL&minus, 1 from adjacent seawater, however, GLB found from natural macroalgal species targeted all tested HAB species (five species), ranging between 105 and 106 CFU g&minus, 1 wet weight in density. These findings provide new ecological insights of GLB at macroalgal beds, and concurrently demonstrate the possible biological control of HABs by artificially introduced Ulva beds.

We recently found that peridinin, which is uniquely present in dinoflagellates, reduced cell viability by inducing apoptosis in human colon cancer cells. Peridinin is also found in edible clams and oysters because the major food sources of those shellfish are phytoplanktons such as dinoflagellates. Little is known, however, about the fate of dietary peridinin and its biological activities in mammals. The aim of the present study was to investigate the enzymatic esterification of xanthophylls, especially peridinin which is uniquely present in dinoflagellates, using differentiated cultures of Caco-2 human intestinal cells. We found that peridinin is converted to peridininol and its fatty acid esters in differentiated Caco-2 cells treated with 5mumol/L peridinin solubilized with mixed micelles. The cell homogenate was also able to deacetylate peridinin and to esterify peridininol. Other xanthophylls, such as fucoxanthin, astaxanthin and zeaxanthin, were also esterified, but at relatively lower rates than peridinin. In this study, we found the enzymatic esterification of xanthophylls in mammalian intestinal cells for the first time. Our results suggest that the esterification of xanthophylls in intestinal cells is dependent on their polarity.

Red tides of Heterocapsa circularisquama have led to serious damage of bivalve aquacultures in western coastal areas of Japan. To understand the whole picture regarding the ecology of this species, it is essential to clarify its overwintering mechanisms. In this study, the population dynamics of H. circularisquama were investigated from February 2004 to November 2005, and overwintering cells were identified for the first time in water columns of Uranouchi Inlet, Kochi Prefecture, Japan. Heterocapsa circularisquama cells were detected by the indirect fluorescent antibody technique using monoclonal antibodies that specifically recognize and react to this species. Vegetative cells were almost always detected from the first observation in February 2004 to November 2005 with temperatures of 10.5-30.6°C. During the period from winter to spring, this species survived in areas with a temperature higher than 10°C. The overwintering cells of H. circularisquama were isolated in March 2004, and identification was made via observation of the morphology and body scales of the cultured cells. These overwintering cells were identified as H. circularisquama and reacted to the monoclonal antibody. These results indicate that H. circularisquama can overwinter and survive throughout the year in a vegetative cell state in Uranouchi Inlet.

Heterocapsa circularisquama is the most noxious dinoflagellate to bivalves such as oysters, short-necked clams and pearl oysters because its red tides have caused major mass mortalities. In order to reduce the negative impacts of H. circularisquama, predictions of red tide occurrences are essential, and hence it is important to grasp its population dynamics. The population dynamics of H. circularisquama, however, have not yet been clarified throughout the year. To precisely monitor population dynamics, the fluorescent antibody technique is effective. We here report on H. circularisquama population dynamics monitored with the indirect fluorescent antibody technique (IFAT) using monoclonal antibodies. Samplings were carried out once a week in summer and twice a month in other seasons at 4 points in Ago Bay, Mie Prefecture, Japan, from April 2001 to March 2005. Direct counting of the cells was also performed using a normal optical microscope. Vegetative cells of H. circularisquama monitored with IFAT were generally detected from late spring (May) to late autumn, and the cell density increased (maximum 2.33×106 cells L-1) during summer. The lowest detection level was 1.33 cells L-1 with IFAT. In contrast, monitoring by counting with a common optical microscope often failed to detect H. circularisquama cells even at a density of 103 cells L-1 or more. Water temperature was significantly correlated to the abundances of H. circularisquama, and the cells were almost always observed at a temperature of 25°C or higher (summer season), and never detected at 10°C or lower (winter and early spring) in Ago Bay. In the waters of the bottom layer, H. circularisquama cells tended to be more abundant with lower dissolved oxygen (DO) values during summer. Thus, the seasonal distribution of H. circularisquama was clarified almost perfectly together with environmental factors in Ago Bay between spring and early winter.

In recent years, cultivation of fish and shellfish possesses an important portion for securing enough seafood all over the world. While, fisheries industry handling fish and shellfish derived from cultivation in addition to natural seafood are exposed to the danger of mass mortality of the reared and toxicities of bivalves, sometimes resulting in serious economic losses and physiological damages by seafood poisoning.

Peridinin, which is uniquely present in dinoflagellates, is one of the most abundant carotenoids found in nature. We evaluated the apoptotic effect of peridinin on DLD-1 human colorectal cancer cells. Peridinin significantly reduced the cell viability in a dose-dependent manner (0-20 microM) and induced apoptosis by activating both caspase-8 and caspase-9. Our findings could be important for the high-performance utilization of marine bioproducts.