Administration of cilostazol, an antiplatelet, to patients with acute-stage cerebral infarction and its effects on plasma substance P level and latent time of swallowing reflex.

BACKGROUND AND OBJECTIVE: It has been reported that medical treatment with cilostazol (cilo) as an antiplatelet may increase a substance P level in the striatum to shorten the latent time of swallowing reflex (LTSR). We undertook a pilot study to confirm whether cilo administration to patients with cerebral infarction is effective in increasing their plasma substance P level and then in ameliorating the status of LTSR. METHODS AND SUBJECTS: Eligible subjects were recruited, after informed consents, from 20 hospitalized patients with acute-phase cerebral infarction within 72 hours from the onset. At the start of treatment, the subjects were assigned at random to those given aspirin alone (non-cilo group) and those given aspirin plus cilo (cilo group). Plasma substance P levels and LTSR values were measured at the starting point (baseline), 28 days after, and 180 days after. RESULTS AND DISCUSSION: No significant time-dependent change in plasma substance P level was found probably because of large individual differences but, 28 days after the start of treatment, this value tended to become higher in cilo group than in non-cilo group (P<0.10). Whereas, in terms of fold changes of LTSR in cilo group, there was a significant between-term difference at P<0.05, indicating that this medication is effective in ameliorating the swallowing function is improved in the long run. CONCLUSION: The LTSR values was significantly shortened within 180 days after the start of cilo treatment, but the result was not well explained by substance P levels as far as these were measured using the plasma, probably because this substance had diluted during blood circulation. However, it will become clinically usable as a single swallowing index, if in the future some ingeneus method of its measurement is developed. A larger-scale study would also be needed to confirm our conclusion from this pilot study.

Effects of eicosapentaenoic acid on asymmetric dimethylarginine in patients in the chronic phase of cerebral infarction: a preliminary study.

BACKGROUND: Eicosapentaenoic acid (EPA) possesses a variety of pharmacologic actions and demonstrates protective efficacy against stroke. Meanwhile, asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide synthase inhibitor and is thereby considered one of the risk factors of cardiovascular disease. The effects of the EPA treatment on ADMA in patients in the chronic phase of cerebral infarction accompanied by dyslipidemia were investigated. METHODS: Study subjects were individuals with either atherothrombotic or lacunar cerebral infarction in the chronic phase accompanied by dyslipidemia, of which the onset was at least 4 weeks earlier. Lipid, fatty acid, and ADMA levels in the blood were measured at EPA 1800 mg per day and compared both before and after treatment. Twenty subjects were included in the study (average age, 71.9 ± 8.9 years). RESULTS: Of these 20 cases, eight were atherothrombotic and 12 were lacunar. Moreover, 17 cases were accompanied by hypertension and 10 cases were accompanied by diabetes mellitus. After EPA treatment (average duration of treatment, 143 ± 42 days), EPA increased from 65.1 ± 38.1 µg/mL to 201.1 ± 73.4 µg/mL (P < .01). Arachidonic acid (AA) decreased from 149.1 ± 34.8 µg/mL to 129.7 ± 22.3 µg/mL (P < .01), and the EPA/AA ratio increased from 0.45 ± 0.26 to 1.55 ± 0.46 (P < .01). ADMA decreased from 0.49 ± 0.07 nmol/mL before treatment to 0.46 ± 0.05 nmol/mL after treatment (P < .01). CONCLUSIONS: EPA treatment in patients in the chronic phase of cerebral infarction leads to a decrease in ADMA in the blood, suggesting that EPA improves vascular endothelial function and therefore supports the protective efficacy against cerebral infarction.

Relationship between heart rate variability using Lorenz plot and sleep level.

In the present study, we propose a new technique for estimating depth of sleep over the whole night using electrocardiogram (ECG) RR intervals (RRIs). We produced a Lorenz plot (LP) using the RRIs recorded during all-night sleep and confirmed that changes in distribution on the LP occur based on changes in sleep stage. To evaluate the changes in these distributions, RRIs are projected a LP on a y = x axis, y = -x axis, and analyzed the shifting of the mean (center C) and standard deviation (area S) for each sleep stage. Analysis interval time was 60 seconds, shifting every second, and we compared heart rate variability (HRV) and sleep level. Center C showed progress toward light sleep levels and area S showed the transition phases toward deep sleep. A concordance rate of 60.1% between the estimated values and actual transitional sleep level was obtained for all-night sleep. Therefore, transitional sleep level can be evaluated based on HRV using the LP.

Estimation of sleep stage in the falling asleep period using a Lorenz plot of ECG RR intervals.

The falling asleep period is the shift from the waking stage to sleep stages 1 and 2. Changes during the falling asleep period can be observed on electroencephalograms (EEGs). In this research, we developed a technique for estimating sleep stage at the falling asleep period without using EEGs. We performed a Lorenz plot (LP) using the intervals between heartbeats, known as electrocardiogram (ECG) RR intervals, of the falling asleep period, and confirmed that changes in the distribution on the LP occur according to changes in sleep stage. To evaluate the changes in these distributions, we projected the LP on y = x axis and y = -x axis, and analyzed the shifting of mean and standard deviation in each sleep stage. The results demonstrated that the distance from the coordinate origin to the mean of distribution became longer as sleep stage deepened, but the variations in the distribution of the LP stabilized. By quantitatively evaluating these phenomena, we proposed two indices of mean (M of LP) and ellipse area (S of LP) of the falling asleep period. Additionally, a multiple regression analysis was done to calculate sleep stage quantitatively, culminating in the derivation of the estimated equation of falling asleep period. Therefore, we could easily estimate the directionality of the sleep stage at the falling asleep period using a LP of ECG RR intervals.

Acute disseminated encephalomyelitis developed after Mycoplasma pneumoniae infection complicating subclinical measles infection.

A 26-year-old man developed acute disseminated encephalomyelitis (ADEM) after Mycoplasma pneumoniae infection, and was admitted after developing disturbed consciousness. Magnetic resonance images revealed lesions in the midbrain, bilateral internal capsules, left corona radiata, white matter of the left occipital lobe, and thoracic spinal cord. He was diagnosed with subclinical measles infection since no anthema was observed despite the fact that his serum and cerebrospinal fluid samples were positive for measles IgM antibodies. ADEM following mixed infection with measles and M. pneumoniae is rare, and it is not clear whether an additional infection with measles influenced the onset of ADEM after M. pneumoniae infection. Symptoms did not improve with steroid or immunoglobulin treatment, but improvement in symptoms was observed after plasmapheresis.

Predicting the fate of acute ischemic lesions using perfusion computed tomography.

OBJECTIVE: To investigate whether the prognosis of ischemic tissues in acute cerebral ischemia can be predicted using perfusion computed tomography-derived parameters and, if so, which are the most useful. METHODS: Perfusion computed tomography was performed on 13 ischemic stroke patients within 6 hours of ischemic onset. The absolute and normalized values of regional cerebral blood flow (rCBF), regional cerebral blood volume, and regional mean transit time (rMTT) and their mirror regions were divided into those that infarcted or survived. Receiver operating characteristic analysis was subsequently conducted for these 3 parameters, and their relationship to the threshold and predictability of infarction were evaluated. RESULTS: Acute ischemic lesions with less than 63% of normal rCBF or more than 220% of rMTT almost invariably led to infarction; moreover, the receiver operating characteristic analysis revealed that both rMTT and rCBF, and their normalized derivatives, were equally predictive of infarction. CONCLUSION: Both rCBF and rMTT can be used to predict the ultimate pathological prognosis of cerebral ischemia. Perfusion computed tomography is a very useful early-stage tool for the assessment of these patients.

Novel insights into FGD3, a putative GEF for Cdc42, that undergoes SCF(FWD1/beta-TrCP)-mediated proteasomal degradation analogous to that of its homologue FGD1 but regulates cell morphology and motility differently from FGD1.

We previously demonstrated that FGD1, the Cdc42 guanine nucleotide exchange factor (GEF) responsible for faciogenital dysplasia, is targeted by the ubiquitin ligase SCF(FWD1/beta-TrCP) upon phosphorylation of two serine residues in its DSGIDS motif and subsequently degraded by the proteasome. Here we show that FGD3, which was identified as a homologue of FGD1 but has been poorly characterized, has conserved the same motif and is down-regulated similarly by SCF(FWD1/beta-TrCP). Although FGD3 and FGD1 share strikingly similar Dbl homology (DH) domains and adjacent pleckstrin homology (PH) domains, both of which are responsible for guanine nucleotide exchange, there also exist remarkable differences in their structures. Indeed, FGD1 and FGD3 induced significantly different morphological changes in HeLa Tet-Off cells: whereas FGD1 induced long finger-like protrusions, FGD3 induced broad sheet-like protrusions when the level of GTP-bound Cdc42 was significantly increased by the inducible expression of FGD3. Furthermore, FGD1 and FGD3 reciprocally regulated cell motility: when inducibly expressed in HeLa Tet-Off cells, FGD1 stimulated cell migration whereas FGD3 inhibited it. Thus we demonstrate that the highly homologous GEFs, FGD1 and FGD3 play different roles to regulate cellular functions but that their intracellular levels are tightly controlled by the same destruction pathway through SCF(FWD1/beta-TrCP).

[Early detection of ischemic lesions in the super-acute phase of ischemic cerebrovascular diseases by imaging].

A thrombolytic agent, recombinant tissue plasminogen activator (rt-PA), was recently approved in Japan for use on patients within 3 hrs of the onset of cerebral infarction. In order to salvage cerebral tissue after an ischemic insult, it is crucial to detect the ischemic lesion before it becomes irreversible and to detect the core and penumbra areas of the lesion for guidance in selecting the suitable therapy. In this symposium we discuss the detection of ischemic lesions using plain CT, perfusion CT, and MRI. In the section on plain CT, we present a typical case with early CT signs. In the section on perfusion CT, we report on the feasibility and limitation of the technique for the diagnosis of acute cerebral infarction. In the section on MRI, we study the usefulness of DWI for the early and highly reliable detection of ischemic stroke.

Granulocyte colony stimulation factor (G-CSF) suppresses interleukin (IL)-12 and/or IL-2 induced interferon (IFN)-gamma production and cytotoxicity of decidual mononuclear cells.

PROBLEM: The placenta is one of the few non-hematopoietic tissues to express granulocyte colony stimulation factor (G-CSF). Placental G-CSF production is considered to be one of the major causes of granulocytosis during pregnancy although its physiological role in pregnancy has not yet been examined. METHOD OF STUDY: The effects of G-CSF on interleukin (IL)-2 and/or IL-12 induced interferon (IFN)-gamma production of magnetic cell sorting (MACS) sorted decidual lymphocytes was examined by enzyme-linked immunosorbent spot-forming cell assay (ELISPOT). The effect of G-CSF on cytotoxicity of decidual lymphocytes against the choriocarcinoma cell line JEG-3 was examined by lactate dehydrogenase (LDH) release assay. RESULTS: As previously reported by us, IL-2 and/or IL-12 activated decidual mononuclear cells were capable of killing choriocarcinoma cells. We observed that G-CSF abolished IFN-gamma production and cytotoxicity of decidual mononuclear cells and MACS sorted CD56+ cells. CONCLUSIONS: In addition to its well-known trophic effects on hematopoiesis, our results suggest about new roles of G-CSF in reproductive immunology.

Effect of glycerol on ischemic cerebral edema assessed by magnetic resonance imaging.

The aim of this study is to assess the anticerebral edema effect of glycerol on a large cerebral infarction with magnetic resonance imaging (MRI). Glycerol, which is widely used as an osmotic agent against cerebral edema, could exacerbate brain tissue shift, since it has been suggested that glycerol might shrink a noninfarcted hemisphere and worsen the mass effect after a large hemispheric cerebral infarction. To investigate these issues, changes in a large hemispheric infarction with cerebral edema were studied using MRI before and after glycerol administration. Infarct volumes, normal brain tissue volumes and lateral ventricle volumes, in addition to signal intensities of T(2)-weighted images, were measured in six patients before and after administration of 300 ml of glycerol. Ventricle volumes were significantly increased (p=0.0015) and the T(2) signal intensity of the post-treatment ischemic region decreased after glycerol administration. In contrast, no significant differences in either cerebral volume or T(2) signal intensity were seen in the noninfarcted hemisphere before and after administration. Our data suggest that glycerol does not exacerbate the mass effect on a large hemispheric infarction.

Use of a Nitrate-Nonutilizing Mutant and Selective Media to Examine Population Dynamics of Fusarium oxysporum f. sp. spinaciae in Soil.

ABSTRACT Determining the population density of the spinach wilt pathogen Fusarium oxysporum f. sp. spinaciae in soil with conventional Fusarium-selective media is quite difficult because nonpathogenic strains of F. oxysporum also grow on those media and are indistinguishable from the pathogen. Therefore, a nitrate-nonutilizing (nit) mutant of the pathogen and corresponding selective media were tested in an experimental approach to determine the population density of the pathogen. Colony forming units of the pathogen were countable after soil-dilution plating onto nit mutant-selective media MMCPA, CMP, and CGMBP. Colony forming units of wild-type Fusarium spp. were countable using a wildtype Fusarium-selective medium, GMBP. By combining nit mutant- and wild-type-selective media, the population densities of pathogenic and nonpathogenic F. oxysporum in the same soil could be measured selectively. This method was useful in studying population dynamics of the pathogen after different soil treatments. Soil disinfested with hot water or chloropicrin was amended with the nit mutant pathogen, and subsequent changes in population densities of the pathogen were compared with those in nontreated field soil. The pathogen rapidly proliferated in disinfested soil and wilt developed faster than in nontreated soil. When a nonpathogenic isolate of F. oxysporum was added at high density to sterilized soil prior to the pathogen, growth of the pathogen was greatly suppressed. Nonpathogenic F. oxysporum could not, however, reduce the density of preexisting pathogen.