Listeriosis is a disease that is induced by infection with the Gram-positive bacterium Listeria monocytogenes. Much is still unknown about the pathogenesis of encephalitic listeriosis. We aimed to identify the contribution of glial fibrillary acidic protein (GFAP), epithelial cadherin (E-cadherin), S100, and acute-phase proteins (APPs) in pathogenesis, clinical and preclinical diagnosis of natural cases of encephalitic listeriosis. Of 1,325 Ossimi sheep, 64 were suspected of having listeriosis from 2018 to 2020. Prospective cohort evaluation of clinical and postmortem findings was performed, in addition to bacterial isolation, the measurement of APPs in serum and cerebrospinal fluid (CSF), and the histopathological and immunohistochemical evaluation of GFAP, S100, and E-cadherin. Infected sheep showed nervous symptoms ranging from neck stretching to complete paralysis. APPs were significantly increased in the CSF of both clinically and preclinically diseased animals; however, serum APPs were only significantly increased in clinically diseased animals. Histopathological evaluation revealed microabscesses, meningoencephalitis, and perivascular cuffing of the brainstem of infected sheep. Immunohistochemical investigations revealed strong expression of GFAP and S100 in necrotic areas and negative expression of E-cadherin. The measurement of CSF APPs could be useful in the preclinical diagnosis of sheep listeriosis. GFAP and S100 proteins could be involved in the pathogenesis of listeriosis; however, E-cadherin does not appear to be involved.

Antidepressant drugs affect monoamines and neuropeptides in human cerebrospinal fluid (CSF) and in rodent brain. The purpose of this study was to investigate if also electroconvulsive therapy (ECT) affects these compounds in a similar manner in the CSF of depressed patients. Homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and corticotropin-releasing hormone (CRH)-like immunoreactivity (-LI) and neuropeptide Y (NPY)-LI were determined in CSF in six drug resistant patients with major depression. Lumbar puncture was performed at baseline and after completion of eight ECTs. ECT was associated with an increase in NPY-LI (p = 0.009) and a decrease in CRH-LI (p ≤ 0.001). HVA (p = 0.003) and 5-HIAA (p = 0.002) were significantly increased after the ECT. Findings of NPY increase and CRH decrease were similar to those following chronic treatment with citalopram, indicating that these changes might constitute one of the common underpinnings of antidepressant treatment modalities.

Over the past 25 years much effort has been put into the research of the relationship between neuropsychiatric disorders and the concentrations of CSF-monoamine metabolites. Most of this research has beenfocused on the relation between CSF-concentrations of 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) and specific symptomatological entities, particularly schizophrenia, Alzheimer's dementia and endogenous depression. It appeared that specific relations between diseases and CSF-concentrations of monoamine metabolites cannot be longer maintained and that a more functional psychopathology should be considered as the future research strategy.

Obstructive hydrocephalus can be treated with an extracranial shunting system or, when the obstruction is between the posterior third ventricle and the fourth ventricular outflow tracts, by an endoscopic third ventriculocisternostomy (ETV). The placement of an extracranial shunting device entails significant long-term risk of infection and malfunction. This risk has led to the concept that ETV is preferable to shunting. While the long-term cognitive performance of shunted hydrocephalus patients has been extensively examined, the outcome of patients undergoing ETV has been studied only sparsely. Ten adults who had undergone ETV were entered into the study under institutional review board approval. Each patient underwent a neuropsychological testing battery that included testing within the domains of basic attention, verbal memory, visual memory, language, and executive functioning. Aggregate test scores showed a decrease in performance in the domains of memory and executive functioning when compared to normative data. The present study revealed persistent cognitive inefficiencies in memory and executive domains in patients post-ETV intervention. A larger longitudinal study considering the impact of prior shunting, presence of headaches, emotional status, and surgical complications will assist in elucidating the etiology and eventual treatment of these deficits. (JINS, 2009, 15, 394–398.)

Fresh cytosols extracted from unfertilised eggs of Xenopus laevis contain a cytostatic factor (CSF) which arrests the cell cycle at metaphase when microinjected into cleaving blastomeres. This CSF is sensitive to Ca2+ and is designated primary CSF (1°CSF). During storage of Ca2+-containing cytosols at 2°C, a stable CSF activity appears which is designated secondary CSF (2°CSF). In the present study, we report that 2°CSF activity can be induced in cytosols extracted from stage VI oocytes, unfertilised eggs, electrically activated eggs or blastulae, in the presence of Ca2+. Both the intensity and the rate of 2°CSF development are dependent on the concentration of Ca2+ ions added to the cytosol. At Ca2+ concentrations of 5–10 mM, 2°CSF activity reaches a maximum in about 7 days. Secondary CSF is relatively resistant to heat but loses all activity after 5 min at 70°C. When stored at −80°C, 2°CSF activity remains detectable for about 6 weeks. Cytological observations show that blastomeres arrested by microinjection of 2°CSF developed in cytosols of unfertilised eggs, activated eggs or blastulae contain metaphase chromosomes embedded in a bipolar spindle that has no asters developed at its poles. In contrast, blastomeres arrested by 2°CSF in cytosols of stage VI oocytes contain condensed chromosomes but no spindle is formed. The mechanisms of the development of 2°CSF in Ca2+-containing cytosols and its mode of action are discussed.

ABSTRACT

Background: Tramiprosate (3-amino-1-propanesulfonic acid, 3APS, ALZHEMED™) is an investigational product candidate that is believed to reduce amyloid deposition in the brain by binding to soluble Aβ, thereby slowing or halting the progression of Alzheimer Disease (AD). Design and Methods: We assessed the safety, tolerability, and pharmacokinetic/pharmacodynamic profiles of tramiprosate in a randomized, double-blind, placebo-controlled Phase II study in which 58 subjects with mild-to-moderate AD were randomly assigned to receive placebo or tramiprosate 50, 100, or 150 mg BID for 3 months. At the end of the double-blind study, 42 of these patients entered an open-label extension study in which they received tramiprosate 150 mg BID for an additional 17 months. Assessments included plasma and CSF tramiprosate concentrations, CSF Aβ42 concentrations, and psychometric tests (Alzheimer's Disease Assessment Scale – cognitive subscale, Mini-Mental State Examination, and Clinical Dementia Rating Scale – Sum of Boxes). Results: Tramiprosate had no significant impact on vital signs or laboratory test values. The most frequent side effects were nausea, vomiting, and diarrhea, which were intermittent and mild-to-moderate in severity. Overall, six tramiprosate-treated patients discontinued because of side effects (all causalities) and there were no drug-related serious adverse events. Tramiprosate crossed the blood–brain barrier and dose-dependently reduced CSF Aβ42 levels after 3 months of treatment. There were no psychometric score differences between treatment groups after 3 months of double-blind treatment. However, psychometric score changes over the 17-month open-label extension study are consistent with a slowing of cognitive and clinical decline, particularly in mild subjects. Interpretation: Long-term administration of tramiprosate is safe and tolerated in patients with mild-to-moderate AD. The short-term reduction of CSF Aβ42 levels and the long-term open-label cognitive and clinical assessments are consistent with disease-modification.

We show that in contrast to metaphase II oocytes, metaphase I oocytes cannot be activated by fusion with the zygote. Fusion of metaphase I oocytes with G2 zygotes was followed by premature chromosome condensation, with 60% of the hybrids becoming arrested at metaphase I, the remainder progressing and arresting at metaphase II. Hybrids of metaphase I oocytes and M-phase zygotes underwent accelerated maturation, but all arrested at metaphase II. In both cases the arrest could be overcome by treatment with the parthenogenetic activators ethanol and cycloheximide. We discuss these findings in relation to the possibility that the metaphase I oocyte contains cytostatic factor activity that is activated by its zygotic partner. Alternatively, the G2 zygote may provide an inhibitor of anaphase, normally never present in the metaphase I oocyte and which is absent from the M-phase zygote.

Prion diseases of humans and other animals have clinical, economic and political significance. Pre-mortem diagnosis is therefore of great importance. Clinical diagnostic criteria and the current status of the available diagnostic tests are reviewed and possible future developments discussed. Presently, most diagnostic tests are indirect, relying on findings that may not be confined to prion diseases rather than on their particular intrinsic nature. They are therefore not absolutely specific nor are they 100% sensitive. The electroencephalogram (EEG), cerebral imaging and cerebrospinal fluid (CSF) analysis are the main techniques employed. However, there is hope that useful blood tests could be developed which would be simpler and less invasive. Also, there is hope that more specific tests will become available.