A multicenter study of transient global amnesia for the better detection of magnetic resonance imaging abnormalities.

BACKGROUND AND PURPOSE: The detection rate of diffusion-weighted (DWI) hyperintense lesions varies widely in patients with transient global amnesia (TGA). The aim was to examine the association of hyperintense lesions on DWI magnetic resonance imaging (MRI) with patient characteristics, precipitating factors, clinical presentation and MRI settings in patients with TGA. METHODS: In this multicenter retrospective observational study, using the standardized diagnosis entry system of electronic health records of four tertiary medical centers in the Kansai district of Japan, TGA patients (n = 261) who underwent brain MRI within 28 days of onset were examined. When the onset time was unavailable, the discovery time was used. RESULTS: Diffusion-weighted hyperintense lesions were observed in 79 patients (30%). There were no significant differences in age, sex, vascular risk factors, precipitating factors or clinical presentation between patients with and without DWI lesions. The detection rate increased linearly 24 h after onset and then reached a plateau of 60%-80% by 84 h. After 84 h, the detection rate decreased rapidly. In a multivariate logistic regression model, MRI examination 24-84 h after onset (odds ratio 7.00, 95% confidence interval 3.50-13.99) and a thin-slice (≤3 mm) DWI sequence (odds ratio 7.59, 95% confidence interval 3.05-18.88) were independent predictors of DWI lesions. CONCLUSIONS: This study suggests that DWI hyperintense lesions in TGA are not associated with patient characteristics and clinical presentation. Brain MRI examination 24-84 h after onset and thin-slice DWI sequences enhance the detection of DWI lesions in TGA patients.

Carotid artery disease in post-stroke survivors and effects of enriched environment on stroke pathology in a mouse model of carotid artery stenosis.

AIMS: Carotid artery disease (CAD) is an important risk factor for stroke. We first evaluated CAD and stroke pathology in elderly post-stroke survivors. To simulate CAD, we assessed long-term consequences of bilateral common carotid artery stenosis (BCAS) in mice and exposed them to environmental enrichment (EE). METHODS: Histopathological methods were used to determine degrees of CAD (% area stenosis), brain infarct types, sizes and distribution in post-stroke survivors and BCAS mice. Adult male C57BL/6J mice after BCAS or sham surgery were randomly assigned to standard housing (Std) or limited (3 h) or full-time (Full) exposure to EE per day for 12 weeks. RESULTS: High frequencies of moderate carotid artery stenosis (51-75%) were evident in post-stroke survivors whereas those with severe CAD (>75% stenosis) exhibited greater numbers of cortical rather than subcortical infarcts and, were at higher risk of developing dementia. BCAS in mice reduced cerebral blood flow by 52% (P < 0.01) and thickened carotid artery walls, regardless of EE duration. Remarkably, the total and cortical infarcts declined by >50% in BCAS mice exposed to EE compared with BCAS-Std (P < 0.01). Frontal lobe and cortical strokes were associated with worsening working memory tested in a radial maze paradigm. Proteomic analysis revealed EE, both BCAS-3 h and BCAS-Full attenuated coagulation cascade factors including fibrinogen and von Willebrand factor, markers of blood-brain barrier damage. CONCLUSION: Small cortical and subcortical infarcts were evident in both post-stroke survivors with CAD and BCAS mice. Experimental evidence suggested that moderate exposure to EE is sufficient to reduce subsequent stroke lesions.

Improvement of virus removal by pilot-scale coagulation-ultrafiltration process for wastewater reclamation: Effect of optimization of pH in secondary effluent.

Reclaimed water (i.e., reused advanced-treated wastewater) offers an alternative water resource. To reduce the health risks associated with its use, efficient virus removal such as with advanced wastewater treatment processes is important. Virus removal by coagulation followed by ultrafiltration (UF) for the treatment of drinking water has been well examined. But its efficacy in wastewater reclamation purpose using secondary treated effluent (SE) from wastewater treatment plant (WWTP) as feed water is unclear. Here, we optimized the virus removal efficiency of coagulation-UF in pilot-scale wastewater reclamation plants using SE as feed water, using the F-specific RNA bacteriophage MS2 as a model virus, at two wastewater treatment plants in Japan. We investigated how using coagulation as a pretreatment for UF improved virus removal efficiency. The efficiency varied greatly between SEs. To reveal the cause of the variation, we conducted laboratory-scale batch coagulation experiments. The efficiency of viral coagulation was negatively correlated with the concentration of dissolved organic matter in the feed water. The optimum pH for coagulation differed between SEs, and the efficiency of coagulation could be dramatically improved by optimizing the pH. We confirmed that the virus removal efficiency in the pilot-scale facility actually could be improved by adjusting the pH. In addition, we confirmed that coagulation-sedimentation-UF with pH adjustment could operate stably for more than 30 days at the pilot scale, with a high virus removal rate. Thus, the wastewater reclamation process described here offers promise in terms of reduced health risks and practical operation.

Relationship between Cnm-positive Streptococcus mutans and cerebral microbleeds in humans.

OBJECTIVE: Cerebral hemorrhage has been shown to occur in animals experimentally infected with Streptococcus mutans carrying the collagen-binding Cnm gene. However, the relationship between cerebral microbleeds and oral hygiene, with a focus on Cnm gene-positive S. mutans infection, remains unclear. MATERIAL AND METHODS: One hundred and thirty-nine subjects participated. The presence or absence of Cnm-positive S. mutans and its collagen-binding activity were investigated using saliva samples, and relationship with cerebral microbleeds detected on MRI investigated, including clinical information and oral parameters. RESULTS: Fifty-one subjects were identified as Cnm-positive S. mutans carriers (36.7%), with cerebral microbleeds being detected in 43 (30.9%). A significantly larger number of subjects carried Cnm-positive S. mutans in the cerebral microbleeds (+) group. S. mutans with Cnm collagen-binding ability was detected in 39 (28.1%) of all subjects, and the adjusted odds ratio for cerebral microbleeds in the Cnm-positive group was 14.4. Regarding the presence of cerebral microbleeds, no significant differences were noted in the number of remaining teeth, dental caries, or in classic arteriosclerosis risk factors. CONCLUSIONS: The occurrence of cerebral microbleeds was higher in subjects carrying Cnm-positive S. mutans, indicating that the presence of Cnm-positive S. mutans increases cerebral microbleeds, and is an independent risk for the development of cerebrovascular disorders.

Effects of intravenous administration of umbilical cord blood CD34(+) cells in a mouse model of neonatal stroke.

Neonatal stroke occurs in approximately 1/4000 live births and results in life-long neurological impairments: e.g., cerebral palsy. Currently, there is no evidence-based specific treatment for neonates with stroke. Several studies have reported the benefits of umbilical cord blood (UCB) cell treatment in rodent models of neonatal brain injury. However, all of the studies examined the effects of administering either the UCB mononuclear cell fraction or UCB-derived mesenchymal stem cells in neonatal rat models. The objective of this study was to examine the effects of human UCB CD34(+) cells (hematopoietic stem cell/endothelial progenitor cells) in a mouse model of neonatal stroke, which we recently developed. On postnatal day 12, immunocompromized (SCID) mice underwent permanent occlusion of the left middle cerebral artery (MCAO). Forty-eight hours after MCAO, human UCB CD34(+) cells (1×10(5)cells) were injected intravenously into the mice. The area in which cerebral blood flow (CBF) was maintained was temporarily larger in the cell-treated group than in the phosphate-buffered saline (PBS)-treated group at 24h after treatment. With cell treatment, the percent loss of ipsilateral hemispheric volume was significantly ameliorated (21.5±1.9%) compared with the PBS group (25.6±5.1%) when assessed at 7weeks after MCAO. The cell-treated group did not exhibit significant differences from the PBS group in either rotarod (238±46s in the sham-surgery group, 175±49s in the PBS group, 203±54s in the cell-treated group) or open-field tests. The intravenous administration of human UCB CD34(+) cells modestly reduced histological ischemic brain damage after neonatal stroke in mice, with a transient augmentation of CBF in the peri-infarct area.

Visualization of lenticulostriate arteries by flow-sensitive black-blood MR angiography on a 1.5 T MRI system: a comparative study between subjects with and without stroke.

BACKGROUND AND PURPOSE: The branches of the LSA are the main causative arteries for lacunar infarction, though the vascular changes are largely unknown. Herein, we examined the correlation of LSA imaging findings in patients with lacunar infarction compared with controls by using FSBB-MRA. MATERIALS AND METHODS: Fifteen patients (9 men, 6 women; mean age, 73 years) with infarction at the basal ganglia and/or its vicinity were prospectively enrolled, and 12 aged-matched control subjects (6 men, 6 women; mean age, 68 years) were examined by using FSBB-MRA on a 1.5T MR imaging system. Total number and length of visualized LSA branches were compared by a 2-tailed 2-sample t test. Stepwise multiple regression analyses were performed, including hypertension, hyperlipidemia, smoking history, and diabetes mellitus after evaluation of their colinearity. P<.05 after correction for multiple comparisons was considered significant. RESULTS: Patients with stroke had significantly fewer LSA branches (average, 6.3; 95% CI, 5.4-7.1) than controls (8.7; 95% CI, 7.8-9.5) (P=.0003). The total LSA lengths were 117 mm (95% CI, 96-138 mm) for patients with stroke and 162 mm (95% CI, 133-91 mm) for control subjects (P=.01). In stepwise multiple regression analysis, only the LSA branch numbers were significantly related to infarction (P=.0003), while only hypertension was significantly related to total LSA length (P=.0085). CONCLUSIONS: Using FSBB-MRA to visualize LSA branches, we found a significant reduction in the numbers of LSA branches in patients with stroke, and hypertension was inversely related to total LSA length. FSBB is a promising method to investigate the LSA by using 1.5T MR imaging.

Percepción de docentes y alumnos sobre documentos Odontológicos legales utilizados en la práctica clínica de Facultades de Odontología del Paraguay año 2011 / Perception of teachers and students on legal documents used in the Dental Clinical Practice of Dental Schools in Paraguay in 2011

El odontólogo tiene grandes responsabilidades en la sociedad, en función de la misma existen normas éticas y legales que le dan un norte a ese profesional. Todas las actividades odontológicas deben ser plasmadas en documentaciones que son el medio por el cual se demuestra la actuación del mismo. La confección del consentimiento informado es obligatoria según los Códigos Penal y Sanitario y la historia clínica lo es para asegurar una medicina de calidad. El mejor lugar para impartir esta enseñanza es la facultad durante la formación del estudiante. Se evaluó la percepción de docentes y estudiantes sobre documentos odontológicos legales utilizados en la práctica clínica de Facultades del Paraguay con el propósito de tomar medidas correctivas necesarias inculcando el verdadero objetivo de estos documentos en la Institución. Es un estudio observacional descriptivo y componente analítico, se aplicó un cuestionario auto administrado a 233 sujetos. Se observó percepción del 63%; sólo el 3% considera la confección del consentimiento informado como un acto médico y el 92% cree necesario un centro de admisión de pacientes en su Institución. No se observó significancia estadística en relación del tipo de Institución pública o privada y la percepción sobre los documentos odontológicos p= 0,1 p> 0,05

Association of vascular parkinsonism with impaired neuronal integrity in the striatum.

The purpose of this study is to identify the underlying differences between patients with white matter lesions (WMLs) who manifested gait disturbance suggestive of vascular parkinsonism (VaP) and those who did not, using the PET scan. Fourteen patients with extensive WMLs, as determined by MRI, were divided into two groups - 7 with gait disturbance and 7 without it. Neuronal integrity was evaluated with a PET scan using [(11)C]flumazenil (FMZ) by calculating the distribution volume of FMZ (FMZ-V(d)) in various regions of interest by non-linear curve fitting. Additionally, tracer kinetic analysis was applied for voxel-by-voxel quantification of FMZ-V(d) and data analysis was performed using statistical parametric mapping. The striatal FMZ-V(d) values were inversely correlated with the motor UPDRS scores (r = 0.70, p < 0.005), and their reductions were associated with the presence of gait disturbance. Therefore, differences in neuronal integrity in the striatum may determine whether patients with WMLs develop VaP or not.

Subinsular vascular lesions: an analysis of 119 consecutive autopsied brains.

The insula of Reil constitutes a functionally intriguing complex of the brain related to multifunctional activities. We examined the subinsular region in 119 consecutively autopsied patients, as T2 hyperintense lesions are frequently observed in magnetic resonance diagnosis of this region. The patients were admitted in neurology wards and were diagnosed as having cerebrovascular disease in 55 patients (46%), other neurological diseases in 57 patients (48%) and non-neurological diseases in seven patients (6%). Demyelination of the white matter was semi-quantified as a fiber density score (percent stained area/total area) with computer-assisted image analysis on Klüver-Barrera-stained sections. Astrogliosis was assessed by immunohistochemistry for glial fibrillary acidic protein. The lesion analysis showed a dilated perivascular space in 29 patients (24%), demyelination (fiber density score less than the mean - 1 SD) in 27 patients (23%), slit-shaped lesion in six patients (5%), lacunar infarction in one patient (1%) and cerebral hemorrhage in one patient (1%). A histologic-radiologic comparison in two patients with subcortical ischemic vascular dementia showed correspondence between subinsular hyperintensities, and demyelination, gliosis and a dilated perivascular space. These results indicate that subinsular lesions rarely signifies focal vascular lesions, and are consisted of demyelination, gliosis and a dilated perivascular space.

Functional characterization of Musca glutamate- and GABA-gated chloride channels expressed independently and coexpressed in Xenopus oocytes.

Ligand-gated chloride channels (LGICs) are important targets for insecticides and parasiticides. Genes encoding subunits of two LGICs, a glutamate-gated chloride channel (MdGluCl-alpha) and a gamma-aminobutyric acid (GABA)-gated chloride channel (MdRdl), were cloned from house-flies (Musca domestica L.). These genes were first expressed independently in Xenopus laevis oocytes by cRNA injection in order to investigate the pharmacology of these ligand-gated channels using two-electrode voltage-clamp electrophysiology. It was found that L-glutamate and GABA activated the MdGluCl-alpha homo-oligomers with an EC(50) value of 30 microM and the MdRdl homo-oligomers with an EC(50) value of 101 microM, respectively. Both channels were chloride ion-permeable, and the MdRdl channel was more sensitive to chloride channel blockers, such as gamma-hexachlorocyclohexane (gamma-HCH), fipronil and picrotoxinin, than the MdGluCl-alpha channel. MdGluCl-alpha required only 1-2 days of incubation after cRNA injection to be expressed in oocytes, whereas 4-7 days of incubation was necessary to achieve MdRdl expression. However, when the cRNA of MdGluCl-alpha was injected at a dose of 1% (w/w) 1 day after the injection of the cRNA of MdRdl, a significant increase in the current amplitude of responses to GABA was observed, and the incubation period necessary for MdRdl expression became shorter. These results suggest that MdGluCl-alpha assists in the expression of MdRdl when the two are coexpressed.

Decrease in cortical benzodiazepine receptors in symptomatic patients with leukoaraiosis: a positron emission tomography study.

BACKGROUND AND PURPOSE: [11C]flumazenil (FMZ), a ligand that selectively binds to the central benzodiazepine receptor in the neuronal membrane, is useful for evaluating neuronal viability in a positron emission tomography (PET) scan. Using this ligand, we investigated whether there was a correlation between neuronal integrity in various brain structures and dementia in patients with leukoaraiosis. METHODS: Twelve patients with extensive leukoaraiosis on magnetic resonance imaging were divided into groups of patients with or without dementia. Based on a 2-compartment, 2-parameter model that included metabolite-corrected arterial input and PET-measured cerebral radioactivity, the distribution volume of FMZ (FMZ-V(d)) was calculated in various regions of interest by nonlinear curve fitting. Additionally, tracer kinetic analysis was applied for voxel-by-voxel quantification of FMZ-V(d), and data analysis was performed by statistical parametric mapping. RESULTS: The presence of dementia was associated with a reduced FMZ-V(d) in widespread areas of the cerebral cortex, including the bilateral frontopolar and frontal/insular areas, the left temporo-occipital border areas, and the left marginal cortical areas. CONCLUSIONS: Differences in neuronal integrity in the cerebral cortex might determine whether patients with leukoaraiosis become symptomatic or not.

Chronic cerebral hypoperfusion induces white matter lesions and loss of oligodendroglia with DNA fragmentation in the rat.

Cerebrovascular white matter lesions represent an age-related neurodegenerative condition that appears as a hyperintense signal on magnetic resonance images. These lesions are frequently observed in aging, hypertension and cerebrovascular disease, and are responsible for cognitive decline and gait disorders in the elderly population. In humans, cerebrovascular white matter lesions are accompanied by apoptosis of oligodendroglia, and have been thought to be caused by chronic cerebral ischemia. In the present study, we tested whether chronic cerebral hypoperfusion induces white matter lesions and apoptosis of oligodendroglia in the rat. Doppler flow meter analysis revealed an immediate reduction of cerebral blood flow ranging from 30% to 40% of that before operation; this remained at 52-64% between 7 and 30 days after operation. Transferrin-immunoreactive oligodendroglia decreased in number and the myelin became degenerated in the medial corpus callosum at 7 days and thereafter. Using the TUNEL method, the number of cells showing DNA fragmentation increased three- to eightfold between 3 and 30 days post-surgery compared to sham-operated animals. Double labeling with TUNEL and immunohistochemistry for markers of either astroglia or oligodendroglia showed that DNA fragmentation occurred in both of these glia. Messenger RNA for caspase-3 increased approximately twofold versus the sham-operated rats between 1 and 30 days post-surgery. Immunohistochemistry revealed up-regulation of caspase-3 in the oligodendroglia of the white matter, and also in the astroglia and neurons of the gray matter. Molecules involved in apoptotic signaling such as TNF-alpha and Bax were also up-regulated in glial cells. These results indicate that chronic cerebral hypoperfusion induces white matter degeneration in association with DNA fragmentation in oligodendroglia.

Neuroleptic malignant syndrome with prolonged catatonia in a dopa-responsive dystonia patient.

The authors describe a patient with dopa-responsive dystonia who developed neuroleptic malignant syndrome with prolonged catatonia following treatment with neuroleptic agents. Use of these agents probably expanded the patient's neuronal dysfunction beyond the nigrostriatal system to involve multiple dopaminergic systems. Electroconvulsive treatment alleviated the prolonged catatonia.

Induction of DNA double strand breaks in scid cells by carbon ions.

The DNA double strand breaks (DSBs) induced by X ray and carbon ion beam irradiation in scid cells were analysed using pulsed-field gel electrophoresis. Scid cells and hybrid cells were ideal to study the DNA DSB repair mechanisms, because their genetic backgrounds were identical except DNA-PK activity. Induction of DNA DSBs was determined after exposure to X rays and carbon beams. DNA DSB repair was by biphasic kinetics with a fast and a slow component. For scid cells only a slow component was observed, whereas the kinetics of DSBs repair was biphasic with a fast and a slow component. It was concluded from the experimental data that the induced DSB rejoining in scid cells was due to the lack of DNA-PK activity.

Analysis of glucose tolerance in twin gestations using an oral glucose load.

The effect of twin gestation on carbohydrate metabolism was evaluated using a 75 g oral glucose tolerance test (75 g OGTT). A 75 g OGTT was performed in 63 twin gestations and 3 791 singleton gestations during the third trimester. Plasma glucose concentrations were measured in the pregnant women under fasting conditions as well as 30 min, 1 h, and 2 h after ingestion of glucose (75 g oral load), and serum insulin concentrations were measured in fasting and 30 min post-ingestion samples. Women with twin gestations showed significantly lower plasma glucose concentrations during fasting and 30 min after the glucose load in the samples taken than those with singleton gestations. No significant difference in serum glucose concentrations was found in the other specimens. There were no cases of gestational diabetes mellitus in our study. Although women with twin gestations demonstrated lower plasma glucose concentrations than women with singleton gestations, the difference observed was subtle. We could not find any significant differences in these plasma glucose values as used to define a pathologic OGTT between twin and singleton pregnancies, with the exception of the fasting value.

Insecticidal and neural activities of candidate photoaffinity probes for neonicotinoid binding sites.

Photoreactive derivatives of imidacloprid and its nitromethylene analogue were synthesized as candidate photoaffinity probes for identifying the amino acid residues of nicotinic acetylcholine receptors (nAChRs) that interact with the neonicotinoid insecticides. When the candidate probes were injected into American cockroaches, the nerve cord neural activity initially increased, then ceased and death of the insect followed. Both the nerve cord and toxicity were enhanced by changing the photoreactive substituent from the para position to the meta position on the spacer benzyl moiety. When tested on a Drosophila SAD/chicken beta2 hybrid, recombinant nAChR expressed in Xenopus oocytes, the nitromethylene candidate probes showed agonist activity similar to that previously observed for imidacloprid.

Chronic cerebral hypoperfusion induces MMP-2 but not MMP-9 expression in the microglia and vascular endothelium of white matter.

White matter lesions are closely associated with cognitive impairment and motor dysfunction in the aged. To explore the pathophysiology of these lesions, the authors examined the expression of matrix metalloproteinase-2 (MMP-2) and MMP-9 in the white matter in a rat model of chronic cerebral hypoperfusion. After bilateral clipping of the common carotid arteries, myelin staining revealed demyelinating changes in the optic tract and the corpus callosum on day 7. Zymographic analyses indicated an increase in the level of MMP-2, but not MMP-9, after the hypoperfusion. Immunohistochemical analyses revealed the presence (most abundantly on day 3) of MMP-2-expressing activated microglia in the optic tract and corpus callosum. In contrast, the capillary endothelial cells expressed MMP-2 later. IgM-immunoreactive glial cells were absent in the sham-operated animals, but were present in the hypoperfused animals by day 3, reflecting the disrupted blood-brain barrier. These findings suggest that the main sources of the elevated MMP-2 were the microglia and the endothelium, and that these cells may contribute to the remodeling of the white matter myelin and microvascular beds in chronic cerebral hypoperfusion.

hOGG1 exon7 polymorphism and gastric cancer in case-control studies of Japanese Brazilians and non-Japanese Brazilians.

Polymorphism of hOGG1 may be capable of serving as a genetic marker for individual susceptibility to various cancers because of its role in the repair of oxyradical DNA damage. We examined the distribution of the hOGG1 Ser326Cys polymorphism and its presumed correlation with gastric cancer risk in two case-control studies of different ethnic groups in São Paulo, Brazil. Potentially eligible Japanese (JB) and non-Japanese Brazilian (NJB) case subjects were defined as patients with newly diagnosed malignant neoplasms of the stomach in 13 hospitals in São Paulo. Ninety-six JBs and 236 NJBs were adopted as subjects. Two controls were matched for each JB case, and one control for each NJB case. The subjects were interviewed using a questionnaire and their blood samples were collected. A significant difference in the distribution of this polymorphism between the two ethnic groups was observed (chi(2)=58.3, P<0.01). The mutant type (Ser/Cys or Cys/Cys) was predominant (approximately 65%) in the JBs, but was only present in approximately 40% of the NJBs. Logistic regression analysis showed no significant increased risk for either the Ser/Cys or Cys/Cys type in either group. The odds ratios of the Cys allele for gastric cancer were 1.01 (95% confidence interval (CI): 0.52-1.93) in the JBs and 0.85 (95% CI: 0.57-1.26) in the NJBs. In the NJBs, a significant increased risk of smoking was shown only in the Ser/Ser type, and no increased risk was shown in the genotypes with the Cys allele. However, no statistically significant interactions were observed with smoking or other possible confounding factors. No statistically significant difference in the distribution of the polymorphism was observed between the intestinal type and diffuse type of gastric cancer in either the JBs or the NJBs. The ethnic difference in hOGG1 Ser326Cys polymorphism was much greater than the case-control difference, and this polymorphism is unlikely to be associated with gastric cancer.