The detection of the IgM antibody for the dengue virus in serum by ELISA has become one of the most important and useful methods for diagnosis of dengue using a single acute-phase serum sample. ...Currently, this system is an invaluable tool for the surveillance of dengue fever (DF) and dengue hemorrhagic fever (DHF). The usefulness of other serological markers such as IgA and IgE have been less studied.
To study the IgM, IgA and IgE specific antibody response in dengue 3 infected patients with different clinical picture and type of infection.
One hundred and twenty-seven serum samples collected on days 5–7 at the onset of fever from clinically and serologically confirmed dengue cases were studied. Forty-two were classified as primary dengue fever cases, 48 as secondary dengue fever cases and 37 as secondary dengue hemorrhagic fever cases. All samples were tested by capture ELISA in order to detect dengue IgM, IgA and IgE antibodies.
In this study, significant differences were observed in the IgM, IgA and IgE response between the study groups. High IgA and IgE OD ratios in secondary dengue cases were found. The usefulness of serotype specific IgM antibody detection is also analyzed and discussed. A priority for future dengue research in terms of protection, recovery of infection and immunopathogenesis is to elucidate the role of these immunoglobulins. The cross reactivity response to IgM between dengue virus serotypes in primary and secondary cases should also be more studied.
Reactive astrocytes are astrocytes undergoing morphological, molecular, and functional remodeling in response to injury, disease, or infection of the CNS. Although this remodeling was first described ...over a century ago, uncertainties and controversies remain regarding the contribution of reactive astrocytes to CNS diseases, repair, and aging. It is also unclear whether fixed categories of reactive astrocytes exist and, if so, how to identify them. We point out the shortcomings of binary divisions of reactive astrocytes into good-vs-bad, neurotoxic-vs-neuroprotective or A1-vs-A2. We advocate, instead, that research on reactive astrocytes include assessment of multiple molecular and functional parameters-preferably in vivo-plus multivariate statistics and determination of impact on pathological hallmarks in relevant models. These guidelines may spur the discovery of astrocyte-based biomarkers as well as astrocyte-targeting therapies that abrogate detrimental actions of reactive astrocytes, potentiate their neuro- and glioprotective actions, and restore or augment their homeostatic, modulatory, and defensive functions.
Objective We aimed to design and validate a quantitative method for clinical assessment of pantothenate kinase associated neurodegeneration (PKAN). Methods Cross-sectional multicenter study of PKAN ...patients recruited through professional associations. Design of a Disease Rating Scale for PKAN (PKAN-DRS) including five sub-scales: cognitive, behavioral, dystonia, parkinsonism, other neurological signs and disability. Items were scored from 0 to 3–4 (maximum severity), (total scores 0–125). For validity and reliability assessment, three independent examiners rated PKAN patients using recorded videotapes. Sanger sequencing of NBIA genes was performed in unsolved NBIA families. Results 13 PKAN patients (mean age 32 years, range 8–77) were assessed through the PKAN-DRS (scores 29–71). Higher scores were obtained in the following items: postural instability, bradikinesia and freezing (parkinson subscale); jaw-tongue, lower face, foot and hand (dystonia subscale); gait and speech (other neurologic signs). Spearman correlation tests showed significant positive correlations between disability and physical scores. Age at diagnosis correlated negatively with dystonia and positively with Parkinsonism. Parkinsonism and disability increased significantly with disease duration. The ICCs for inter-observer agreement was considered “almost perfect” (ICC=0.97), with an internal reliability when all subscales are included considered as “good” (Cronbach's alpha = 0.85). Regarding inter-item evaluation, reliability was considered “good” for dystonia, parkinsonism and disability sub-scores (0.87, 0.82 and 0.88, respectively) and “poor” for other neurological signs (0.20). Six homozygous p. T528M gipsy patients obtained lower PKAN-DRS scores for all subscales when compared with the group of patients with other mutations. Conclusion The proposed PKAN-DRS seems a reliable method to assess the more prevalent neurologic signs in PKAN. Dystonia was more severe in patients with an earlier disease onset, predominating in the jaw and tongue and in the distal limbs. Atypical parkinsonism worsened with disease duration. Haplotype studies are necessary to search for a possible founder effect of the mutation p. T528M in our population.
Objectives Thiamine transporter-2 (hTHTR2) deficiency due to SLC19A3 mutations is a potentially reversible cause of Leigh syndrome for which no biochemical markers are currently available. Our aim ...was to assess the sensitivity of thiamine quantification in cerebrospinal fluid (CSF) and fibroblasts from patients with Leigh encephalopathy and SLC19A3 defects as compared with other causes of Leigh syndrome. Methods Thiamine vitamers (free-thiamine, thiamine monophosphate (TMP) and thiamine diphosphate (TDP)) were analyzed by HPLC-fluorescence detection in whole-blood and cerebrospinal fluid (CSF) samples from 106 and 38 paediatric controls, respectively. Results were compared with patients with Leigh syndrome due to SLC19A3 defects (N=6) and mitochondrial respiratory chain defects (N=9). In all but one SLC19A3 patient, samples were collected before thiamine supplementation. Thiamine vitamers were also analyzed by HPLC in fibroblasts from SLC19A3 patients (N=3) and patients with other metabolic defects (N=6). Results A negative correlation between thiamine isoforms and age was detected in whole-blood and CSF, thus three reference intervals were established for free-thiamine and two intervals for TMP and TDP. Free-thiamine was severely reduced in five non-treated SLC19A3 patients CSF, but not TMP and TPP. The SLC19A3 patient under thiamine supplementation showed thiamine values above reference range. Nine Leigh patients with mitochondrial defects showed normal o slightly reduced values for CSF thiamine. In SLC19A3 patient's fibroblasts, a reduction in free-thiamine was detected as compared with control sample. These values normalized after thiamine was added to the culture medium. Conclusion SLC19A3 patients show a profound deficiency of free-thiamine in the CSF that allows their identification from other causes of Leigh syndrome. SLC19A3 is essential to maintain CSF thiamine homeostasis and to prevent brain damage. Thiamine overload can supply the SLC19A3 defect and restore thiamine values in fibroblasts and CSF, probably by an alternative transport system.
PDF
