Chung, Suk-Jae;Ramanathan, Vikram;Brett, Claire M.;Giacomini, Kathleen M.
Journal of Pharmaceutical Investigation
/
v.25
no.3
/
pp.7-20
/
1995
Taurine, a ${\beta}-amino$ acid, plays an important role as a neuromodulator and is necessary for the normal development of the brain. Since de novo synthesis of taurine in the brain is minimal and in vivo studies suggest that taurine dose not cross the blood-brain barrier, we examined whether the choroid plexus, the blood-cerebrospinal fluid (CSF) barrier, plays a role in taurine transport in the central nervous system. The uptake of $[^3H]-taurine$ into ATP depleted choroid plexus from rabbit was substantially greater in the presence of an inwardly directed $Na^+$ gradient taurine accumulation was negligible. A transient in side-negative potential gradient enhanced the $Na^+-driven$ uptake of taurine into the tissue slices, suggesting that the transport process is electrogenic, $Na^+-driven$ taurine uptake was saturable with an estimated $V_{max}$ of $111\;{\pm}\;20.2\;nmole/g/15\;min$ and a $K_M\;of\;99.8{\pm}29.9\;{\mu}M$. The estimated coupling ratio of $Na^+$ and taurine was $1.80\;{\pm}\;0.122.$$Na^+-dependent$ taurine uptake was significantly inhibited by ${\beta}-amino$ acids, but not by ${\alpha}-amino$ acids, indicating that the transporter is selective for ${\beta}-amino$ acids. Since it is known that the physiological concentration of taurine in the CSF is lower than that in the plasma, the active transport system we characterized may face the brush border (i.e., CSF facing) side of the choroid plexus and actively transport taurine out of the CSF. Therefore, we examined in vivo elimination of taurine from the CSF in the rat to determine whether elimination kinetics of taurine from the CSF is consistent with the in vitro study. Using a stereotaxic device, cannulaes were placed into the lateral ventricle and the cisterna magna of the rat. Radio-labelled taurine and inulin (a marker of CSF flow) were injected into the lateral ventricle, and the concentrations of the labelled compounds in the CSF were monitored for upto 3 hrs in the cisterna magna. The apparent clearance of taurine from CSF was greater than the estimated CSF flow (p<0.005) indicating that there is a clearance process in addition to the CSF flow. Taurine distribution into the choroid plexus was at least 10 fold higher than that found in other brain areas (e. g., cerebellum, olfactory bulb and cortex). When unlabelled taurine was co-administered with radio-labelled taurine, the apparent clearance of taurine was reduced (p<0.0l), suggesting a saturable disposition of taurine from CSF. Distribution of taurine into the choroid plexus, cerebellum, olfactory bulb and cortex was similarly diminished, indicating that the saturable uptake of taurine into these tissues is responsible for the non-linear disposition. A pharmacokinetic model involving first order elimination and saturable distribution described these data adequately. The Michaelis-Menten rate constant estimated from in vivo elimination study is similar to that obtained in the in vitro uptake experiment. Collectively, our results demonstrate that taurine is transported in the choroid plexus via a $Na^+-dependent,saturable$ and apparently ${\beta}-amino$ acid selective mechanism. This process may be functionally relevant to taurine homeostasis in the brain.
Purpose : Refractory status epilepticus(RSE) is a serious neurological emergency in children. The mortality is high and the neurological outcome is not good. This study aimed to evaluate the clinical significance of cerebrospinal fluid(CSF) pleocytosis in refractory status epilepticus in children. Methods : From January 1999 to January 2006, 25 out of 37 children with refractory status epilepticus had spinal tapping. We retrospectively analyzed the data from these children's medical records. We compared the results between groups with and without CSF pleocytosis, and between a group with first seizure and a group with epilepsy. Result : Six out of 25 children had CSF pleocytosis. The group without CSF pleocytosis had a higher mortality rate and required higher doses of antiepileptic drugs as compared with the group with CSF pleocytosis. The group with CSF pleocytosis had much worse neurologic segualae. However, except for the children with CNS infection, the overall prognosis between the group with and without CSF pleocytosis was not significantly different. All children with CSF pleocytosis came in with first seizures. Conclusion : In children with RSE, a CSF study must be perfomed as soon as possible to exclude the possibility of CNS infection. A CSF study is even more important in cases of first seizure or CNS infection suspected. Mild CSF pleocytosis without evidence of infection does not seem to affect the prognosis, so physicians should therefore be more cautious in selecting antibacterial or antiviral agents for it.
Sunagawa, Katsunori;Weisinger, Richard S.;McKinley, Michael J.;Purcell, Brett S.;Thomson, Craig;Burns, Peta L.
Asian-Australasian Journal of Animal Sciences
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v.14
no.4
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pp.467-473
/
2001
The internal humoral factors in the central regulation of dry feed intake during water deprivation in sheep were investigated by measurement of cerebrospinal fluid (CSF) constituents. Five animals were fed dried alfalfa chaff for 2 hours once a day. Sheep in the water deprivation treatment were deprived of water for 28 hours, while the sheep in the control treatment were given free access to water. During the first hour of the 2 hour feeding period, a rapid reduction in blood volume occured in both treatments (water deprivation and free access to water). The CSF concentrations of Na, Cl and osmolality during the second hour of the 2 hour feeding period in both treatments were greater (p<0.01) than those during the first hour. The drinking behaviors in sheep were concentrated during the second hour of the 2 hour feeding period in periods of free access to water. Water intake during feeding in periods of free access to water was 1110 ml/2 h. The levels of increase in CSF osmolality with feeding during water deprivation were greater (p<0.01) than during periods of free access to water. The changes in CSF osmolality with feeding during water deprivation produced more vigorous thirst sensations in the brain compared to during periods of free access to water. The eating rates for the first hour of the allotted 2 hour feeding period were the same under both treatments. However, the eating rates for the second hour during water deprivation periods decreased significantly (p<0.05) compared to those during periods of free access to water. The decreased eating rates for the second hour during water deprivation may be due to the vigorous thirst sensations produced in the brain. The results suggest that the increase in CSF osmolality with feeding during water deprivation acts as a thirst and satiety factor in brain mechanisms controlling feeding to decrease dry feed intake in water-deprived sheep.
Recently, many suggestions have been made in image segmentation methods for extracting human organs or disease affected area from huge amounts of medical image datasets. However, images from some areas, such as brain, which have multiple structures with ambiruous structural borders, have limitations in their structural segmentation. To address this problem, clustering technique which classifies voxels into finite number of clusters is often employed. This, however, has its drawback, the influence from noise, which is caused from voxel by voxel operations. Therefore, applying image enhancing method to minimize the influence from noise and to make clearer image borders would allow more robust structural segmentation. This research proposes an efficient structural segmentation method by filtering based clustering to extract detail structures such as white matter, gray matter and cerebrospinal fluid from brain MR. First, coherence enhancing diffusion filtering is adopted to make clearer borders between structures and to reduce the noises in them. To the enhanced images from this process, fuzzy c-means clustering method was applied, conducting structural segmentation by assigning corresponding cluster index to the structure containing each voxel. The suggested structural segmentation method, in comparison with existing ones with clustering using Gaussian or general anisotropic diffusion filtering, showed enhanced accuracy which was determined by how much it agreed with the manual segmentation results. Moreover, by suggesting fine segmentation method on the border area with reproducible results and minimized manual task, it provides efficient diagnostic support for morphological abnormalities in brain.
Park, Hae-Kyung;Woo, So-Youn;Kim, Hyun-Jin;Chong, Young-Hae
The Journal of Korean Society of Virology
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v.30
no.3
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pp.171-178
/
2000
Herpes simplex virus, Varicella zoster virus and Human herpes virus-6 caused central nervous system infections and latent infections but there is no data of the 3 viruses being tested from the same cerebrospinal fluid samples with aseptic meningitis or encephalitis in adults patients. These viruses produced similar neurologic symptoms but difficulties existed in differentiating of etiologic agents and therefore the viruses needed to be detected in the early state. Herpes simplex virus encephalitis (HSVE) in adults, if not treated promptly was fatal. If treated with antiviral drugs in the early phase of encephalitis, neurologic sequales decreased by 65%. Recently, a PCR method for detection of HSVE with CSF was developed. VZV primary and secondary infections caused neurologic symptoms of encephalitis or meningitis. The second frequency of adult encephalitis that caused VZV were reported. HHV-6 caused CNS latent infection that was studied with normal adults brains. But there is no data of HSV, VZV and HHV-6 for aseptic meningitis and encephalitis of Korean adults through etiologic study. We cultured CSFs on HEp-2 cells and simultaneously tested for HSV PCR, VZV nested PCR and HHV-6 PCR with 8 specific primers. The PCR results of CSF from meningitis Korean adults were 13/19 (68.4%) for HSV, 10/19 (52.6%) for VZV and 12/19 (63.2%) for HHV-67/19 (36.8%) cases were triple infected HSV PCR, VZV PCR and HHV-6 PCR positive; 3/19 (15.8%) cases were dual infected HSV PCR and HHV-6 PCR positive; 1119 (0.5%) cases was VZV PCR positive. Strong viral DNA amplification of CSF means a causative virus may be present in aseptic meningitis or encephalitis patients and may cause clinical neurologic symptoms. HSV and HHV-6 viruses detection rate were higher than VZV by PCR with CSFs.
Objective : The diagnosis of shunt malfunction can be challenging since neuroimaging results are not always correlated with clinical outcomes. The purpose of this study was to evaluate the efficacy of a simple, minimally invasive cerebrospinal fluid (CSF) lumbar tapping test that predicts shunt under-drainage in hydrocephalus patients. Methods : We retrospectively reviewed the clinical and radiological features of 48 patients who underwent routine CSF lumbar tapping after ventriculoperitoneal shunt (VPS) operation using a programmable shunting device. We compared shunt valve opening pressure and CSF lumbar tapping pressure to check under-drainage. Results : The mean pressure difference between valve opening pressure and CSF lumbar tapping pressure of all patients were $2.21{\pm}24.57mmH_2O$. The frequency of CSF lumbar tapping was $2.06{\pm}1.26times$. Eighty five times lumbar tapping of 41 patients showed that their VPS function was normal which was consistent with clinical improvement and decreased ventricle size on computed tomography scan. The mean pressure difference in these patients was $-3.69{\pm}19.20mmH_2O$. The mean frequency of CSF lumbar tapping was $2.07{\pm}1.25times$. Fourteen cases of 10 patients revealed suspected VPS malfunction which were consistent with radiological results and clinical symptoms, defined as changes in ventricle size and no clinical improvement. The mean pressure difference was $38.07{\pm}23.58mmH_2O$. The mean frequency of CSF lumbar tapping was $1.44{\pm}1.01times$. Pressure difference greater than $35mmH_2O$ was shown in 2.35% of the normal VPS function group (2 of 85) whereas it was shown in 64.29% of the suspected VPS malfunction group (9 of 14). The difference was statistically significant (p=0.000001). Among 10 patients with under-drainage, 5 patients underwent shunt revision. The causes of the shunt malfunction included 3 cases of proximal occlusion and 2 cases of distal obstruction and valve malfunction. Conclusion : Under-drainage of CSF should be suspected if CSF lumbar tapping pressure is $35mmH_2O$ higher than the valve opening pressure and shunt malfunction evaluation or adjustment of the valve opening pressure should be made.
Purpose: Meningitis is an acute childhood infection caused by viral or bacterial infection. The purpose of the present study is to analyze the differences between enteroviral meningitis and non-enteroviral aseptic meningitis. Methods: From January 2013 to December 2016, we retrospectively reviewed the medical records of a total of 303 aseptic meningitis patients who visited Wonju Severance Christian Hospital. We examined demographics of all patients and analyzed serologic and cerebrospinal fluid tests, clinical symptoms, and outcomes. Results: Of a total of 303 patients, 197(65.0%) were male, and the most cases occurred from June to November (91.8%). The most common pathogen of meningitis was found to be enterovirus (65.0%). According to the etiology, the enteroviral meningitis group had significantly more headache and enteric symptoms (P=0.0003 and P=0.0013, respectively). Furthermore, the non-enteroviral meningitis group showed pleocytosis in the cerebrospinal fluid and a significantly higher rate of seizure at 1 to 4 years (P=0.0360 and P=0.0002, respectively). Conclusion: In this study, enteroviral meningitis was the most common and the prognosis was good. When compared between two groups, neurological symptoms were frequent in patients with non-enteroviral meningitis in groups 1 to 4 years.
Changes in glutamatergic nervous activities following intracerebroventricular (icv) administration of ethylcholine aziridinium (AF64A) were studied in rats. The levels of total glutamate, those of glutamate in cerebrospinal fluid (CSF) and in extracellular fluid (ECF) of striatum, the activities of glutamine synthetase (GS), glutaminase and glutamate dehydrogenase (GDH) and the specific binding sites of $[^3H]$MK801 in striatum, hippocampus and frontal cortex were assessed a week after the infusion of AF64A (3 nmol) into lateral ventricle. The levels of total glutamate were significantly decreased in striatum, hippocampus and frontal cortex after AF64A treatment. Although the levels of glutamate in CSF weren't changed after AF64A treatment, the levels of glutamate in ECF of striatum were significantly decreased (62.6%). GS activities in striatum were significantly decreased. But, glutaminase activities in striatum were significantly increased. However, the activities of GS and glutaminase in frontal cortex and hippocampus weren't changed. Although GDH activities in frontal cortex were significantly decreased, those in striatum and hippocampus weren't altered. The striatal densities of $[^3H]$MK 801 binding sites were increased without changes in its affinity. Also, the specific binding sites of $[^3H]$MK801 were increased in frontal cortex but not in hippocampus. These results indicate that the glutamatergic nervous activities were altered with the infusion of AF64A into lateral ventricle. Furthermore, it suggest that the decreased levels of glutamate after AF64A treatment may affect the change in the other parameters of glutamatergic neuronal activities.
Objectives We aimed to identify the neuroimaging marker for prediction of the use of atypical antipsychotics (AAP) in dementia patients. Methods From April 2010 to March 2013, 31 patients who were diagnosed as dementia at the psychiatric department of Soonchunhyang University Hospital, completed the brain magnetic resonance imaging scan and cognitive test for dementia. Ten patients were treated with AAP for the improvement of behavioral and psychological symptoms of dementia (BPSD) and the other 21patients were not. Using T1 weighted and Fluid Attenuated Inversion Recovery (FLAIR) images of brain, areas of white matter (WM), gray matter (GM), cerebrospinal fluid (CSF) and white matter hyperintensities (WMH) have been segmented and measured. Multivariate logistic regression models were applied for assessment of association between AAP use and the GM/WM ratio, the WMH/whole brain (GM + WM + CSF) ratio. Results There was a significant association between AAP use and the GM/WM ratio (odds ratio, OR = 1.18, 95% confidence interval, CI 1.01-1.38, p = 0.037), while there was no association between AAP use and the WMH/whole brain ratio (OR = 0.82, 95% CI 0.27-2.48, p = 0.73). Conclusions The GM/WM ratio could be a biological marker for the prediction of AAP use and BPSD in patients with dementia. It was more likely to increase as dementia progress since atrophy of WM was more prominent than that of GM over aging.
The applicability of indirect immunoftuorescent antibody test (IFAT) was compared with enzyme-linked immunosorbent assay (ELISA) in sera from 163 cases of confirmed neurocysticercosis, 101 other neurologic and parasitic diseases and 100 normal controls. As antigen, frozen sections of a Taenia solium metacestode from a human brain was used in IFAT and cystic fluid was used in ELISA. For the detection of specific IgG antibody, IFAT was equally sensitive (89.6%) and specific (85.1%) as ELISA. The antibody titers by IFAT were correspondingly increased with mean absorbance of ELISA. The corresponding rate of positivity in the two techniques was 90.8%. Except for the difficulty in detecting antibodies in cerebrospinal fluid (CSF), IFAT was concluded to be very useful for the serodiagnosis of human neurocysticercosis.
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