123 research outputs found
Is It Lupus? Is It Neuromyelitis Optica Spectrum Disorder (NMOSD)? : Why Not Both?
Multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) are among
the commonly considered differential diagnoses in patients with inflammatory central nervous system (CNS)-diseases. Formerly diagnosed competing autoimmune diseases might impair diagnostics
and treatment. Here, we report on a 41-year-old woman admitted to our hospital with primary
manifestation of NMOSD (paresthesia, paralysis of the lower extremities, and urinary incontinence)
while undergoing treatment for a diagnosed systemic lupus erythematosus (SLE) with hydroxychloroquine. CNS manifestation of the disease was considered. Magnetic resonance imaging (MRI)
of the cranium and spinal cord showed multiple supratentorial lesions of the white matter and
massive intramedullary lesions with contrast enhancement. Cerebrospinal fluid (CSF) showed pleocytosis (20/µL), positive antinuclear antibodies (ANA), antiphospholipid antibodies, and SSA/Ro
antibodies, while formerly positive dsDNA antibodies were negative. Further diagnostics revealed
a 1:10,240 serum titer of Aquaporine-4 antibodies. The patient received intravenous methylprednisolone for three days (2 g per day), which led to an escalation to plasmapheresis and to an improved
EDSS from 8.0 to 4.0. Because of the comorbidity, a combined relapse prophylaxis with satralizumab
and mycophenolate mofetil was established. Rehabilitation and continued treatment improved
EDSS to 1.0 with no impairment of mobilization. Although formerly diagnosed SLE could have
explained the symptoms, it is important to reconsider competitive diseases in order to establish
adequate immunotherap
The Effects of Vitamin D Deficiency on Neurodegenerative Diseases
Approximately 90% of the elderly population in the western countries has at least a mild to moderate vitamin D hypovitaminosis. Besides the well-known function of vitamin D in calcium homeostasis, it has been recently found that several enzymes and receptors involved in its homeostasis are expressed in the nervous system and brain suggesting also an important role in the brain homeostasis. Interestingly, epidemiological and clinical studies found reduced vitamin D level associated with an increased risk of several neurodegenerative disorders. In this chapter, we focus on a potential link between vitamin D and Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, prion disease, and motor neuron disease. Epidemiological studies were summarized, an overview of the known potential underlying pathomolecular mechanisms are given, and results from clinical studies dealing with vitamin D supplementation were presented. As an outlook, recent literature suggesting an impact of vitamin D on autism spectrum disease, depression, and schizophrenia are briefly discussed. In conclusion, the identification of an abundant vitamin D metabolism in the brain and the tight link between the increasing number of several neurological and mental disorders emphasize the need of further research making a clear recommendation of the intake and supplementation of vitamin D in a growing elderly population
Serodiagnosis of bovine besnoitiosis by ELISA and immunofluorescence tests
Sera from non-infected cattle and cattle infected with Anaplasma, Babesia, Theileria and Sarcocystis were tested for antibodies to Besnoitia in ELISA and immunofluorescence tests (IFT) with Besnoitia besnoiti of blue wildebeest origin as antigen. Only 2 out of 86 sera gave false positive reactions in ELISA and none in the IFT, indicating a high specificity for the tests. Three-hundred-and-three bovine sera from 3 farms in an area endemic for besnoitiosis were similarly tested and the results were correlated with clinical findings based on visual inspection for typical symptoms and the presence of cysts in the scleral conjunctiva. Most of the positive tests were observed in cattle older than 1 year. Of the cases with scleral cysts, 68,7% were positive in the ELISA and 81,74% in the IFT. However, 45,74% (ELlSA) and 49,47% (IFT) of the clinically negative cattle were clinically positive, indicating a high incidence of clinically inapparent infection. These results indicate a relatively low sensitivity for these serological tests. An unexpected finding was that the ELISA remained negative for at least 60 days after experimental infection of the cattle, the maximum period for which tests were done, whereas the IFT became positive. No antibodies against B. besnoiti could be found in human sera. Besnoitia jellisoni antigen gave positive results with B. besnoili antibodies in ELISA, but not in the IFT.The articles have been scanned in colour with a HP Scanjet 5590; 600dpi.
Adobe Acrobat XI Pro was used to OCR the text and also for the merging and conversion to the final presentation PDF-format.am201
Who acquires infection from whom and how? Disentangling multi-host and multi-mode transmission dynamics in the 'elimination' era
Multi-host infectious agents challenge our abilities to understand, predict and manage disease dynamics. Within this, many infectious agents are also able to use, simultaneously or sequentially, multiple modes of transmission. Furthermore, the relative importance of different host species and modes can itself be dynamic, with potential for switches and shifts in host range and/ or transmission mode in response to changing selective pressures, such as those imposed by disease control interventions. The epidemiology of such multi-host, multi-mode infectious agents thereby can involve a multi-faceted community of definitive and intermediate/secondary hosts or vectors, often together with infectious stages in the environment, all of which may represent potential targets, as well as specific challenges, particularly where disease elimination is proposed. Here, we explore, focusing on examples fromboth human and animal pathogen systems, why and how we should aim to disentangle and quantify the relative importance of multi-host multi-mode infectious agent transmission dynamics under contrasting conditions, and ultimately, how this can be used to help achieve efficient and effective disease control.
This article is part of the themed issue 'Opening the black box: re-examining the ecology and evolution of parasite transmission'
Gemfibrozil-Induced Intracellular Triglyceride Increase in SH-SY5Y, HEK and Calu-3 Cells
Gemfibrozil is a drug that has been used for over 40 years to lower triglycerides in blood.
As a ligand for peroxisome proliferative-activated receptor-alpha (PPARα), which is expressed in
many tissues, it induces the transcription of numerous genes for carbohydrate and lipid-metabolism.
However, nothing is known about how intracellular lipid-homeostasis and, in particular, triglycerides
are affected. As triglycerides are stored in lipid-droplets, which are known to be associated with many
diseases, such as Alzheimer’s disease, cancer, fatty liver disease and type-2 diabetes, treatment with
gemfibrozil could adversely affect these diseases. To address the question whether gemfibrozil also
affects intracellular lipid-levels, SH-SY5Y, HEK and Calu-3 cells, representing three different metabolically active organs (brain, lung and kidney), were incubated with gemfibrozil and subsequently
analyzed semi-quantitatively by mass-spectrometry. Importantly, all cells showed a strong increase
in intracellular triglycerides (SH-SY5Y: 170.3%; HEK: 272.1%; Calu-3: 448.1%), suggesting that the
decreased triglyceride-levels might be due to an enhanced cellular uptake. Besides the common
intracellular triglyceride increase, a cell-line specific alteration in acylcarnitines are found, suggesting
that especially in neuronal cell lines gemfibrozil increases the transport of fatty acids to mitochondria
and therefore increases the turnover of fatty acids for the benefit of additional energy supply, which
could be important in diseases, such as Alzheimer’s disease
Methylxanthines and Neurodegenerative Diseases: An Update
Methylxanthines (MTX) are purine derived xanthine derivatives. Whereas naturally
occurring methylxanthines like caffeine, theophylline or theobromine are widely consumed in food,
several synthetic but also non-synthetic methylxanthines are used as pharmaceuticals, in particular in
treating airway constrictions. Besides the well-established bronchoprotective effects, methylxanthines
are also known to have anti-inflammatory and anti-oxidative properties, mediate changes in lipid
homeostasis and have neuroprotective effects. Known molecular mechanisms include adenosine
receptor antagonism, phosphodiesterase inhibition, effects on the cholinergic system, wnt signaling,
histone deacetylase activation and gene regulation. By affecting several pathways associated with
neurodegenerative diseases via different pleiotropic mechanisms and due to its moderate side
effects, intake of methylxanthines have been suggested to be an interesting approach in dealing with
neurodegeneration. Especially in the past years, the impact of methylxanthines in neurodegenerative
diseases has been extensively studied and several new aspects have been elucidated. In this review
we summarize the findings of methylxanthines linked to Alzheimer´s disease, Parkinson’s disease
and Multiple Sclerosis since 2017, focusing on epidemiological and clinical studies and addressing
the underlying molecular mechanisms in cell culture experiments and animal studies in order to
assess the neuroprotective potential of methylxanthines in these diseases
Unique Role of Caffeine Compared to Other Methylxanthines (Theobromine, Theophylline, Pentoxifylline, Propentofylline) in Regulation of AD Relevant Genes in Neuroblastoma SH-SY5Y Wild Type Cells
Methylxanthines are a group of substances derived from the purine base xanthine with
a methyl group at the nitrogen on position 3 and different residues at the nitrogen on position 1
and 7. They are widely consumed in nutrition and used as pharmaceuticals. Here we investigate
the transcriptional regulation of 83 genes linked to Alzheimer’s disease in the presence of five
methylxanthines, including the most prominent naturally occurring methylxanthines—caffeine,
theophylline and theobromine—and the synthetic methylxanthines pentoxifylline and propentofylline.
Methylxanthine-regulated genes were found in pathways involved in processes including oxidative
stress, lipid homeostasis, signal transduction, transcriptional regulation, as well as pathways involved
in neuronal function. Interestingly, multivariate analysis revealed different or inverse effects on gene
regulation for caffeine compared to the other methylxanthines, which was further substantiated by
multiple comparison analysis, pointing out a distinct role for caffeine in gene regulation. Our results
not only underline the beneficial effects of methylxanthines in the regulation of genes in neuroblastoma
wild-type cells linked to neurodegenerative diseases in general, but also demonstrate that individual
methylxanthines like caffeine mediate unique or inverse expression patterns. This suggests that the
replacement of single methylxanthines by others could result in unexpected effects, which could not
be anticipated by the comparison to other substances in this substance class
Effect of Caffeine and Other Methylxanthines on Aβ-Homeostasis in SH-SY5Y Cells
Methylxanthines (MTX) are alkaloids derived from the purine-base xanthine.
Whereas especially caffeine, the most prominent known MTX, has been formerly assessed to
be detrimental, this point of view has changed substantially. MTXs are discussed to have beneficial
properties in neurodegenerative diseases, however, the mechanisms of action are not completely
understood. Here we investigate the effect of the naturally occurring caffeine, theobromine
and theophylline and the synthetic propentofylline and pentoxifylline on processes involved in
Alzheimer’s disease (AD). All MTXs decreased amyloid-β (Aβ) level by shifting the amyloid precursor
protein (APP) processing from the Aβ-producing amyloidogenic to the non-amyloidogenic pathway.
The α-secretase activity was elevated whereas β-secretase activity was decreased. Breaking down
the molecular mechanism, caffeine increased protein stability of the major α-secretase ADAM10,
downregulated BACE1 expression and directly decreased β-secretase activity. Additionally, APP
expression was reduced. In line with literature, MTXs reduced oxidative stress, decreased cholesterol
and a decreased in Aβ1-42 aggregation. In conclusion, all MTXs act via the pleiotropic mechanism
resulting in decreased Aβ and show beneficial properties with respect to AD in neuroblastoma cells.
However, the observed effect strength was moderate, suggesting that MTXs should be integrated in a
healthy diet rather than be used exclusively to treat or prevent AD
Transorbital sonography and MRI reliability to assess optic nerve sheath diameter in idiopathic intracranial hypertension
Background and Purpose: The purpose of this study was to evaluate the performance of
magnetic resonance imaging (MRI) in measuring the optic nerve sheath diameter (ONSD)
compared to the established method transorbital sonography (TOS) in patients with
idiopathic intracranial hypertension (IIH).
Methods: Twenty-three patients with IIH were prospectively included applying IIH
diagnostic criteria. All patients received a lumbar puncture with assessment of the cerebrospinal fluid (CSF) opening pressure to assure the IIH diagnosis. Measurement of ONSD
was performed 3 mm posterior to inner sclera surface in B-TOS by an expert examiner, while three independent neuroradiologists took measurements in axial T-weighted
MRI examinations. The sella turcica with the pituitary gland (and potential presence of
an empty sella) and the trigeminal cavity were also assessed on sagittal and transversal
T1-weighted MRI images by one independent neuroradiologist.
Results: The means of ONSD between ultrasound and MRI measurements were 6.3 mm
(standard deviation [SD] = 0.6 mm) and 6.2 mm (SD = 0.8 mm). The interrater reliability
between three neuroradiologists showed a high interclass correlation coefficient (ICC)
(confidence interval: .573 < ICC < .8; p < .001). In patients with an empty sella, the ONSD
evaluated by MRI was 6.6 mm, while measuring 6.1 mm in patients without empty sella.
No correlation between CSF opening pressure and ONSD was found.
Conclusions: MRI can reliably measure ONSD and yields similar results compared to
TOS in patients with IIH. Moreover, patients with empty sella showed significantly larger
ONSD than patients without empty sella
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