We provide concentrations of all B6 vitamers in simultaneously sampled plasmaand CSF ofchildren. Given the ethical concerns, we were unable to obtain CSF samples from healthy chil- dren. Therefore, we used remnant CSF samples that were taken for diagnostic evaluation ofin- tellectual disability, which was in some children accompanied by epilepsy. CSF samples taken for other indications like meningitis or encephalitis are not protected from light or stored at −80°C. Thus, our approach to use remnant samples that were taken and stored under strictly prescribed conditions may be the best option. Children visiting the Sylvia Tóth Center, which is a quaternary diagnostic referral institution for children with intellectual disability, undergo extensive metabolic screening. For most children, this includes determination of amino acids, pipecolic acid, homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), 3-O-methyl- DOPA and 5-methyltetrahydrofolate (5-MTHF) in CSF. It therefore is very likely that, when being the cause of the clinical picture in these children, genetic metabolic disorders associated with a functional deficiency ofvitaminB6 are picked up by these investigations. To our knowl- edge, none of the childrenin our dataset suffered from one of these defects, although we cannot exclude the possibility of an undiagnosed neurometabolic disorder subtly influencing B6 vita- mer concentrations. So although we used plasmaand CSF ofchildren with intellectual disabili- ty, we are confident that our approach provides the best possible reflection of healthy vitaminB6 homeostasis inchildrenand that it enables us to obtain further insight inB6 vitamers and their interrelationships.
Our results showed that CSF miRNAs from MDD patients could be detected. Unfortunately, it is very difficult to obtain CSF from MDD patients by lumber puncture. It is more convenient and easier to use serum specific miRNAs from MDD patients for diagnosis. Therefore, we should seriously consider how to look for serum specific miRNAs as biomarker for MDD be- cause the change of CSF miRNAs was poorly related to the alteration of serum miRNAs for CNS diseases. Serum miRNAs that are consistent with CSF changes of miRNAs should be identified in MDD patients, and these miRNAs from CSF should have relative high serum lev- els and be easily detected in serum. Therefore, Focus 179 microRNA PCR Panels were chosen for the analysis of CSF miRNAs from MDD patients (http://www.Exiqon.com/serum-plasma- miRNA-qPCR). The reasons why we only measured 179 miRNAs instead of performing a mi- croarray for miRNome profiling analysis are as follows: (1) The amount of samples such as serum or CSF is really small, which means that a more sensitive and accurate platform is need- ed. (2) Not all microRNAs could be detected in serum, and we cared about those which may exist in serum. Exiqon has extensive in-house knowledge of microRNA profiling in serum. All 179 miRNA assays have been carefully selected based on Exiqon’s vast number ofin-house analyses of miRNA expression in blood serum andplasma samples as well as on the limited number of peer-reviewed published papers available.
Although different conditions were assayed, we were not able to combine Hcys with the vitamins in the same analytical procedure, and so we proceeded to the optimization of two methods differing only in the composition of the gradient of the mobile phase and the injected volume. It was found that MEPS did not bring any benefit to the quantification of the Hcys in the plasma. Therefore, we developed and validate an alternative method that uses the direct injection of treated plasma (reduced and precipitated). This same method was evaluated in terms of selectivity, linearity, limit of detection (LOD), limit of quantification (LOQ), matrix effect and precision (intra-and inter-day) and applied to the determination of Hcys in a group composed by patients presenting augmented CVD risk. Good results in terms of selectivity and linearity (R 2 > 0.9968) were obtained, being the values of LOD and LOQ 0.007 and 0.21 mol / L, respectively. The intra-day precision (1.23-3.32%), inter-day precision (5.43-6.99%) and the recovery rate (82.5 to 93.1%) of this method were satisfactory. The matrix effect (>120%) was, however, higher than we were waiting for. Using this methodology it was possible to determine the amount of Hcys in real plasma samples from individuals presenting augmented CVD risk. Regarding the methodology developed for vitamins, despite the optimization of the extraction technique and the chromatographic conditions, it was found that the levels usually present inplasma are far below the sensitivity we obtained. Therefore, further optimizations of the methodology developed are needed.
transport, the CSF drug concentrations should have been approximately equivalent to this unbound plasma level. However, the median total CSF raltegravir levels were nearly 4–fold lower. Even ignoring the lower binding in CSF, this suggests limited drug entry or its active transport out of the CSF. Indeed, raltegravir has previously been suggested to be a substrate for P-gp transport . Correlation of CSF raltegravir concentrations with the albumin ratios and CSF albumin concentrations, which provide measures of BBB/BCB permeability, also suggests that these barriers are active in restricting raltegravir entry. The illustrated case (Figure 2) with three LPs during the course of her recovery from CNS infection also presents anecdotal supporting evidence. As her albumin ratio decreased from a very high value of 23.9, her CSF raltegravir levels decreased in close parallel despite an increase inplasma raltegravir on the third sampling. This case also underscores the mixed interactions of raltegravir with the BBB and albumin itself. On the one hand, the albumin ratio serves as an indicator of the BBB disruption that likely enhances entry of raltegravir. On the other hand, since albumin also binds raltegravir, the free level of drug will also decrease proportionally for a given total drug level as the albumin increases. Also, since albumin levels in CSF are about 5 percent of those in blood, the bound concentration in CSF is much lower than that in blood and contributes less to the total measured drug. We did not directly measure the unbound drug fraction in either plasma or CSF.
Concentrations of specific saturated (SAFA), monounsaturated (MUFA) and polyunsaturated (PUFA) FAs inplasmaand CSF are shown in Table 1. As expected, all FA species were by far more abundant inplasma vs. CSF. Of note, except for a-linolenic and docosahexaenoic acid (r = 0.58, P = 0.001; r = 0.48, P = 0.01, respectively), none of the measured FA species were correlated between plasmaand CSF. The association of docosahexaenoic acid between the two compartments is consistent with a recent report in elderly patients demonstrating a positive correlation between the representation of docosahexaenoic acid inplasmaand brain tissue . However, to date supporting data specifically in humans are scarce and limited in their statistical power, which is why these data need to be viewed as preliminary and interpreted with caution. Nevertheless, this association may support the concept that FAs may act as signaling molecules between the CNS and the periphery and implies that specific lipid transport mechanisms exist across the blood brain barrier (BBB). It is believed that FAs enter the CNS by at least two transport mechanisms: diffusion and/or protein-mediated transport. The regulation of these pathways appears to be dependent on chain length and saturation of the substrate which may support the concept that the transfer of FAs across the BBB is highly regulated . To date the exact regulatory mechanism of FA metabolism at the interface of the BBB is not clear. Using deuterium-labeled FAs Edmond has demonstrated that after peripheral injection, linoleic acid is taken up by the brain, however palmitic, stearic and oleic acid are not . The author concludes that the brain is autonomous in producing most lipids. However, others have postulated that FAs enter the brain from the blood . In humans using 11 C-labeled arachidonic acid it was shown that peripherally injected FAs can be visualized (after only 15 min) in cranial images . Nevertheless, brain fatty acid
and is probably not effective as an analgesic technique. Opioids epidurally administered need to diffuse through the dura mater, subarachnoid, and pia mater to gain access to the spinal cord opioid receptors. After epidural administration, alfentanil rapidly diffuses into the CSF and is readily available to penetrate the spinal cord tissue (CODA et al., 1999). This was demonstrated in our study where similar plasmaand CSF concentrations were obtained after 5 minutes of epidural administration. The lower than expected plasma concentrations of alfentanil and its metabolites detected in our study by the ELISA method may have been due to distribution of the drug to other lipid-soluble tissues of the body. Fast diffusion of alfentanil into vascular spaces occurred and produced concentrations of approximately 10ng ml -1 from 10 minutes up to the end of the study at 24
tients 1, 3, 4, and 5) had symptomatic VS. The E-selectin levels in the CSF of these patients were one order of magnitude higher than the average for all other SAH patients at each time point. The mean (± SD) sE- selectin levels in the CSF of the 4 patients with symptomatic VS measured post-SAH at the three time points were 10.8 ± 1.7, 7.1 ± 7.8, and 7.7 ± 6.7 ng/ml. In contrast, the mean (± SD) levels detected at the same time points in the 8 SAH patients without symptomatic VS were 0.5 ± 0.2, 0.6 ± 0.2, and 0.7 ± 0.4 ng/ml. However, among these patients symptomatic VS had no effect on E-selectin levels (P > 0.05), a fact probably due to the small number of patients with SAH included in this study. In addition, no difference in E-selectin levels was observed according to age, sex, initial Glasgow coma scale, HH grade on presentation, Fisher grade on CT, smoking, co-morbidity, initial leu- kocytosis, and Glasgow outcome scale at 6 months after SAH. These findings are con- sistent with the literature but future clinical trials including more patients are needed in order to provide more accurate results.
T-tau was associated with cognitive performance in three domains, but inconsistently so; higher T-tau concentrations was positively associated with verbal and visuospatial functions, but negatively associated with executive functions. Moreover, there was no difference in CSF T-tau between patients and controls. Hence, the value of T-tau as a predictor of cognitive per- formance might be limited. Also, sAPPβ was only associated with performance in one cognitive domain; lower sAPPβ concentrations correlated with decreased speed/attention performance. Furthermore, the more AD specific biomarkers P-tau and Aβ1–42 were not associated with cognitive performance in any cognitive domain. As P-tau and Aβ1–42 are established biomark- ers for current and future cognitive performance in mild cognitive impairment and AD , findings from the current study accords with the study by Jakobsson and colleagues who found no evidence of an Alzheimer like CSF pattern in patients with bipolar disorder . Although there is some evidence that psychiatric disorders may increase the risk of dementia , a neuropathological study found no increase of amyloid plaques or neurofibrillary tangles in post-mortem brain tissues in a sample of psychiatric patients . Hence, it is more likely that the associations between CSF biomarkers and cognitive domains in patients reflect a neurotox- ic state rather than a neurodegenerative process. As the mean age of this sample was relatively low (38 years) we cannot rule out the possibility that neurodegenerative processes are present in an older cohort.
(2 x 2 cm) were obtained after median sternotomy and section of the pericardium at outset of the heart surgeries. The blood and pericardial fluid samples were centrifuged (3220 g for 10 min at 4°C) and the supernatants were stored at -80°C until analysis. The pericardial tissue biopsies were fixed in neutral buffered formalin for 48 hours at room temperature. Patients with haemolytic pericardial fluid samples were not further considered. Analyses were limited to the plasma, pericardial fluidand pericardial tissue biopsy from the same individual patients (N = 37). Routine plasma analyses for HbA1c, lipids, creatinine and high sensitivity C-reactive protein (hsCRP) were performed at the Odense University Hospital clinical bio- chemistry laboratory. Characteristics of the patients were disclosed to the researchers of the pericardial samples after they finalized their data collection. These characteristics are sum- marized in Table 1.
publicly trusted control system, such as SET protocol should be obtained by banks and its availability and function be communicated to consumers (Tan & Thoen, 2001; Suh & Han, 2003). SET protocol was developed to address issues like non-repudiation because it uses public-key cryptography. Banks should also consider the use of trust seals such as DigiCert, VeriSign, BBB Online. MayBank’s privacy seal is displayed on its web site, compared to most other Malaysia banks that do not have or display such web assurance seal in their web site. It is, therefore, no surprise that over 30% of those surveyed used MayBank for their Internet banking transactions in Malaysia. Banks should also launch an awareness campaign to explain to consumers the control system in use in their electronic banking site. The results of this study also suggest that more than 78% of the respondents do not know what a web assurance seal is. About 15% have no knowledge of web seal and more than 66% are not sure of web seal, even if they see one.
A 46-year-old female presented progressive hand tremor at age of 8, associated to cognitive and motor deterioration. She developed incapacitating head tremor and was wheel- chair-bound 12 years after onset. Premature ovarian failure (POF) occurred at 27-year-old. In the last 3 years, head tre- mor became less intense, but she remained with horizontal bidireccional nistagmus.
methylation of cysteine and dynamic oxidation of methionine were used during the database search. LTQ-Orbitrap MS/MS data were first processed by an in-house software DeconMSn to accurately determine the monoisotopic mass and charge state of parent ions, followed by SEQUEST search against the IPI database in the same fashion, except that 0.1-Da tolerance for precursor ion masses and 1-Da tolerance for fragment ion masses were used. A set of criteria considering the cross correlation score (Xcorr) and delta correlation (DCn) values along with tryptic cleavage and charge states were developed using the decoy database approach and applied for filtering the raw data to limit false positive identifications to ,1% at the peptide level[23–25]. For the LTQ-Orbitrap data, the distribution of mass deviation (from the theoretical masses) was first determined as having a standard deviation (s) of 2.05 part per million (ppm), and peptide identifications with mass error of greater than 3s were filtered out[23,25,26]. In general, slightly lower Xcorr cutoff values were used when combined with DCn and the mass error constraint to achieve the same level of false positive rate (,1%). For peptides identified by both LTQ-Orbitrap (IgY14 flow-through fraction) and LTQ (IgY14 bound fraction) analyses, the database matching scores are shown only for the LTQ-Orbitrap analysis, along with their mass errors (Table S1).
Cerebrotendinous xanthomatosis is a rare autosomal recessive hereditary disease that is caused by a mutation in the gene encoding the mitochondrial enzyme sterol 27- hydroxylase (CYP27). The CYP27 gene is located on chromosome 2q35-qter and is responsible for the conversion of cholesterol into cholic and chenodeoxycholic acid. Cerebrotendinous xanthomatosis results in increased levels of serum cholestanol, a cholesterol precursor, and increased deposition of cholestanol and cholesterol in various tissues, especially the lenses, tendons, and the central nervous system. The principal manifestations of Cerebrotendinous xanthomatosis include juvenile cataracts, tendon xantho- mas, and progressive neurological symptoms. 1
Abstract: The study examined the male and female level of access and ownership to land for cassava production in Abia state. The objectives of the study were to describe the socio-economic characteristics of the respondents, determine the differences in quantity of cassava produced by both male and female farmers. A multi-stage random sampling technique was used select 218 respondents. Questionnaire was used for data collection while frequency counts, mean, percentages and Z-test were used in analyzing the data generated. The result shows that the mean age for male and the female were 52.7 and 46.2 years respectively. 94.5% of the male and 97.2% of the female had one form of formal education. The mean household size of the male and the female were 8 and 7 persons per house. The mean farming experiences of the male and female were 16.54 years and 13.26 years respectively. Mean income generated from cassava stand to be (#) 54882.57 and (#) 126082.60 respectively for both male and female. The Z- test analysis result shows that mean farm sizes of the respondents were 2.91 hectares and 2.45 hectares respectively for both male and female. The analysis also showed that there was significant difference between access to farmland of male and the female farmers at t = -2.613 at 5% significant level and cassava output of male and the female at t = -4.764 at 1% significant level. It was therefore recommended that a micro- credit scheme be established by government and nongovernmental organization target mainly on female cassava farmers for purchase of resources for cassava production.
Unlike pleocytosis, increase in CSF protein concentration was not characterized as a consistent alteration. Taking 40 mg/dL to be the maximum physiological limit (Scott, 2004), only a discrete increase in the CSF protein concentration could be observed in nine naturally infected calves (Table 2). According to Mayhew (1989), only four animals presented high concentrations (above 75 mg/dL). Among the experimentally infected calves, only one presented a high concentration at the end of the disease (108 mg/dL at day 19 p.i.). Nonetheless, this case must be considered as an exception due to the long duration of the disease. In fact, most CSF samples presented were colorless and clear and had pH and specific gravity values within physiological ranges (Scott, 2004).