Pro-inflammatory cytokines in cystic glioblastoma: A quantitative study with a comparison with bacterial brain abscesses. With an MRI investigation of displacement and destruction of the brain tissue surrounding a glioblastoma

Cystic glioblastomas are aggressive primary brain tumors that may both destroy and displace the surrounding brain tissue as they grow. The mechanisms underlying these tumors’ destructive effect could include exposure of brain tissue to tumor-derived cytokines, but quantitative cytokine data are lacking. Here, we provide quantitative data on leukocyte markers and cytokines in the cyst fluid from 21 cystic glioblastomas, which we compare to values in 13 brain abscess pus samples. The concentration of macrophage/microglia markers sCD163 and MCP-1 was higher in glioblastoma cyst fluid than in brain abscess pus; lymphocyte marker sCD25 was similar in cyst fluid and pus, whereas neutrophil marker myeloperoxidase was higher in pus. Median cytokine levels in glioblastoma cyst fluid were high (pg/mL): TNF-α: 32, IL-6: 1064, IL-8: 23585, tissue factor: 28, the chemokine CXCL1: 639. These values were not significantly different from values in pus, pointing to a highly pro-inflammatory glioblastoma environment. In contrast, levels of IFN-γ, IL-1β, IL-2, IL-4, IL-10, IL-12, and IL-13 were higher in pus than in glioblastoma cyst fluid. Based on the quantitative data, we show for the first time that the concentrations of cytokines in glioblastoma cyst fluid correlate with blood leukocyte levels, suggesting an important interaction between glioblastomas and the circulation. Preoperative MRI of the cystic glioblastomas confirmed both destruction and displacement of brain tissue, but none of the cytokine levels correlated with degree of brain tissue displacement or peri-tumoral edema, as could be assessed by MRI. We conclude that cystic glioblastomas are highly pro-inflammatory environments that interact with the circulation and that they both displace and destroy brain tissue. These observations point to the need for neuroprotective strategies in glioblastoma therapy, which could include an anti-inflammatory approach

Ecological investigations in the marginal ice zone in the Barents Sea the summers 1979 and 1980

During the summers of l979 and 1980, ecological investigations were carried out in the marginal ice zone in the Barents Sea. In the investigation an attempt is made to follow the development of the production processes, from nutrients via phytoplankton and zooplankton to capelin, in order to map the feeding conditions for the capelin and its variations. The methods used in the field work and most of the results obtained during the two summer seasons are presented by ELLERTSEN -et -al. (1981). In the present report we discuss and summarize the field results so far and compare them with the results from a model. The results show a close relationship between ice melting and recession and a phytoplankton bloom occurring at the ice edge. It seems that the decrease in salinity in the upper few meters due to ice melting produce a sharp increase in water stability. Thereby favourable conditions are created for an intense phytoplankton bloom. This bloom seems to occur somewhat earlier than the spring bloom in the areas of the Barents Sea not covered by ice, where water stability is mainly influenced by the warming of the upper layers. Zooplankton development follows very close that of the phytoplankton, with a bloom starting near the ice edge. The biomass was found to increase with the distance from the edge. This tendency is most clear in the upper layers, where the zooplankton spawning and the development of the zooplankton larvae occur. The main bulk of the zooplankton consisted of the copepod Calanus finmarchicus. The most numerous species was the small copepod Oithona similis. There was a change in age composition of -C. finmarchicus with the distance from the ice, the nauplii and the younger copepodite stages predominating in the north. The younger stages (I-III) were most abundant in the surface layer where they had hatched earlier in the year, while the older stages (IV-V and adult females) had overwintered and predominated in the deeper layer. The stomach contents of 12-18 cm capelin from several stations were investigated. The stomach filling seemed to be related to the plankton density in the sea, with highest filling in areas with much plankton. The species composition in the stomachs roughly corresponded with the plankton composition, with a tendency to a higher numeric percentage of euphausiids and chaetognaths in the stomachs than in the plankton. Near half of the contents, as weight, consisted of calanoid copepods, while the euphausiids, chaetognaths and amphipods made up 30, 10 and 6 per cent of the weight respectively. A model describing the growth of phytoplankton and zooplankton along a north-south section in the Barents Sea is also briefly described. Using ice map data obtained via satellite, several simulation runs have been performed. The dynamics of the phytoplankton growth seems to agree with what we believe it should according to the available data. However, some discrepancies indicate areas that should be further investigated in order to increase our knowledge and improve the model. The zooplankton part of the model produces results that are more questionable. Variations in zooplankton biomass are reasonably calculated whereas the stage distribution does not fit our data. Reasons for this are discussed

Increased CSF levels of aromatic amino acids in hip fracture patients with delirium suggests higher monoaminergic activity

textabstractBackground: To examine whether delirium in hip fracture patients was associated with changes in the levels of amino acids and/or monoamine metabolites in cerebrospinal fluid (CSF) and serum. Methods: In this prospective cohort study, 77 patients admitted with an acute hip fracture to Oslo University Hospital, Norway, were studied. The concentrations of amino acids in CSF and serum were determined by high performance liquid chromatography. The patients were assessed daily for delirium by the Confusion Assessment Method (pre-operatively and post-operative day 1-5 (all) or until discharge (delirious patients)). Pre-fracture dementia status was decided by an expert panel. Serum was collected pre-operatively and CSF immediately before spinal anesthesia. Results: Fifty-three (71 %) hip fracture patients developed delirium. In hip fracture patients without dementia (n = 39), those with delirium had significantly higher CSF levels of tryptophan (40 % higher), tyrosine (60 % higher), phenylalanine (59 % higher) and the monoamine metabolite 5-hydroxyindoleacetate (23 % higher) compared to those without delirium. The same amino acids were also higher in CSF in delirious patients with dementia (n = 38). The correlations between serum and CSF amino acid levels were poor. Conclusion: Higher CSF levels of monoamine precursors in hip fracture patients with delirium suggest a higher monoaminergic activity in the central nervous system during delirium in this patient group

Tetanus: Pathophysiology, Treatment, and the Possibility of Using Botulinum Toxin against Tetanus-Induced Rigidity and Spasms

Tetanus toxin, the product of Clostridium tetani, is the cause of tetanus symptoms. Tetanus toxin is taken up into terminals of lower motor neurons and transported axonally to the spinal cord and/or brainstem. Here the toxin moves trans-synaptically into inhibitory nerve terminals, where vesicular release of inhibitory neurotransmitters becomes blocked, leading to disinhibition of lower motor neurons. Muscle rigidity and spasms ensue, often manifesting as trismus/lockjaw, dysphagia, opistotonus, or rigidity and spasms of respiratory, laryngeal, and abdominal muscles, which may cause respiratory failure. Botulinum toxin, in contrast, largely remains in lower motor neuron terminals, inhibiting acetylcholine release and muscle activity. Therefore, botulinum toxin may reduce tetanus symptoms. Trismus may be treated with botulinum toxin injections into the masseter and temporalis muscles. This should probably be done early in the course of tetanus to reduce the risk of pulmonary aspiration, involuntary tongue biting, anorexia and dental caries. Other muscle groups are also amenable to botulinum toxin treatment. Six tetanus patients have been successfully treated with botulinum toxin A. This review discusses the use of botulinum toxin for tetanus in the context of the pathophysiology, symptomatology, and medical treatment of Clostridium tetani infection

Økologiske undersøkelser nær iskanten i Barentshavet somrene 1979 og 1980

During the summers of l979 and 1980, ecological investigations were carried out in the marginal ice zone in the Barents Sea. In the investigation an attempt is made to follow the development of the production processes, from nutrients via phytoplankton and zooplankton to capelin, in order to map the feeding conditions for the capelin and its variations. The methods used in the field work and most of the results obtained during the two summer seasons are presented by ELLERTSEN -et -al. (1981). In the present report we discuss and summarize the field results so far and compare them with the results from a model. The results show a close relationship between ice melting and recession and a phytoplankton bloom occurring at the ice edge. It seems that the decrease in salinity in the upper few meters due to ice melting produce a sharp increase in water stability. Thereby favourable conditions are created for an intense phytoplankton bloom. This bloom seems to occur somewhat earlier than the spring bloom in the areas of the Barents Sea not covered by ice, where water stability is mainly influenced by the warming of the upper layers. Zooplankton development follows very close that of the phytoplankton, with a bloom starting near the ice edge. The biomass was found to increase with the distance from the edge. This tendency is most clear in the upper layers, where the zooplankton spawning and the development of the zooplankton larvae occur. The main bulk of the zooplankton consisted of the copepod Calanus finmarchicus. The most numerous species was the small copepod Oithona similis. There was a change in age composition of -C. finmarchicus with the distance from the ice, the nauplii and the younger copepodite stages predominating in the north. The younger stages (I-III) were most abundant in the surface layer where they had hatched earlier in the year, while the older stages (IV-V and adult females) had overwintered and predominated in the deeper layer. The stomach contents of 12-18 cm capelin from several stations were investigated. The stomach filling seemed to be related to the plankton density in the sea, with highest filling in areas with much plankton. The species composition in the stomachs roughly corresponded with the plankton composition, with a tendency to a higher numeric percentage of euphausiids and chaetognaths in the stomachs than in the plankton. Near half of the contents, as weight, consisted of calanoid copepods, while the euphausiids, chaetognaths and amphipods made up 30, 10 and 6 per cent of the weight respectively. A model describing the growth of phytoplankton and zooplankton along a north-south section in the Barents Sea is also briefly described. Using ice map data obtained via satellite, several simulation runs have been performed. The dynamics of the phytoplankton growth seems to agree with what we believe it should according to the available data. However, some discrepancies indicate areas that should be further investigated in order to increase our knowledge and improve the model. The zooplankton part of the model produces results that are more questionable. Variations in zooplankton biomass are reasonably calculated whereas the stage distribution does not fit our data. Reasons for this are discussed

Intellectual disability associated with pyridoxine-responsive epilepsies: The need to protect cognitive development

Pyridoxine (vitamin B6)-responsive epilepsies are severe forms of epilepsy that manifest as seizures immediately after birth, sometimes in utero, sometimes months, or years after birth. Seizures may be treated efficiently by life-long supplementation with pyridoxine or its biologically active form, pyridoxal phosphate, but even so patients may become intellectually disabled, for which there currently is no effective treatment. The condition may be caused by mutations in several genes (TNSALP, PIGV, PIGL, PIGO, PNPO, PROSC, ALDH7A1, MOCS2, or ALDH4A1). Mutations in ALDH7A1, MOCS2, and ALDH4A1 entail build-up of reactive aldehydes (α-aminoadipic semialdehyde, γ-glutamic semialdehyde) that may react non-enzymatically with macromolecules of brain cells. Such reactions may alter the function of macromolecules, and they may produce “advanced glycation end products” (AGEs). AGEs trigger inflammation in the brain. This understanding points to aldehyde-quenching, anti-AGE, or anti-inflammatory therapies as possible strategies to protect cognitive development and prevent intellectual disability in affected children. Studies on how aldehydes traverse cell membranes and how they affect brain function could further the development of therapies for patients with pyridoxine-responsive epilepsies

Pro-inflammatory cytokines in cystic glioblastoma: A quantitative study with a comparison with bacterial brain abscesses. With an MRI investigation of displacement and destruction of the brain tissue surrounding a glioblastoma

Cystic glioblastomas are aggressive primary brain tumors that may both destroy and displace the surrounding brain tissue as they grow. The mechanisms underlying these tumors’ destructive effect could include exposure of brain tissue to tumor-derived cytokines, but quantitative cytokine data are lacking. Here, we provide quantitative data on leukocyte markers and cytokines in the cyst fluid from 21 cystic glioblastomas, which we compare to values in 13 brain abscess pus samples. The concentration of macrophage/microglia markers sCD163 and MCP-1 was higher in glioblastoma cyst fluid than in brain abscess pus; lymphocyte marker sCD25 was similar in cyst fluid and pus, whereas neutrophil marker myeloperoxidase was higher in pus. Median cytokine levels in glioblastoma cyst fluid were high (pg/mL): TNF-α: 32, IL-6: 1064, IL-8: 23585, tissue factor: 28, the chemokine CXCL1: 639. These values were not significantly different from values in pus, pointing to a highly pro-inflammatory glioblastoma environment. In contrast, levels of IFN-γ, IL-1β, IL-2, IL-4, IL-10, IL-12, and IL-13 were higher in pus than in glioblastoma cyst fluid. Based on the quantitative data, we show for the first time that the concentrations of cytokines in glioblastoma cyst fluid correlate with blood leukocyte levels, suggesting an important interaction between glioblastomas and the circulation. Preoperative MRI of the cystic glioblastomas confirmed both destruction and displacement of brain tissue, but none of the cytokine levels correlated with degree of brain tissue displacement or peri-tumoral edema, as could be assessed by MRI. We conclude that cystic glioblastomas are highly pro-inflammatory environments that interact with the circulation and that they both displace and destroy brain tissue. These observations point to the need for neuroprotective strategies in glioblastoma therapy, which could include an anti-inflammatory approach

ADHD symptoms and use of anabolic androgenic steroids among male weightlifters

Abstract Use of anabolic androgenic steroids (AAS) is associated with adverse health effects. The factors that predispose to AAS use among athletes are poorly understood, but attention deficit/hyperactivity disorder (ADHD), which is known to occur among athletes more often than in the general population, is associated with risk behaviors, including substance abuse. We aimed to see if AAS use in male weightlifters was associated with ADHD symptoms, and test the link between ADHD symptoms and cognitive performance. Hundred and forty male weightlifters, 72 AAS users and 68 weightlifting controls (WLC), completed the Achenbach system of empirically based assessment (ASEBA) for ADHD symptoms and underwent cognitive examination. Self-reported ADHD symptom scores were significantly higher among AAS users compared to WLC, and scores in the range indicating clinically important ADHD was significantly more common in the AAS-using group. Age of onset of AAS use correlated inversely with ADHD scale score (r = − 0.35; p = 0.003). ADHD score correlated inversely with cognitive scores for working memory (r = − 0.25, p < 0.001), processing speed (r = − 0.24, p < 0.001), verbal learning and memory (r = − 0.19, p = 0.03), and problem solving (r = − 0.20, p = 0.02). AAS use among weightlifters is associated with ADHD symptoms and corresponding lower cognitive performance. Recognising a relationship between ADHD symptoms and AAS use may guide drug prevention strategies in sports