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Otoneurologic disturbances caused by solvent pollution.

Subjects exposed to industrial solvents may experience vertigo and nausea. Solvents are usually volatile hydrocarbon compounds, which are important parts of everyday life in a modern society. They may also cause neurastenia, personality changes, and reduced intellectual capacity. The syndrome that may develop was formerly named psycho-organic syndrome (POS), but in modern terminology it is called chronic toxic encephalopathy (CTE). The syndrome develops slowly, and during the first years no pathological findings will be found using various test batteries. Somewhat later, when the syndrome still might be reversible, psychometric, auditory, and otoneurologic testing may well unveil disturbances within the posterior fossa structures. Animal experiments suggest one site of effect for solvents to be within the cerebellum and brainstem regions with close relationship to the gamma-amino-butyric acid (GABA) transmission. In the otoneurologic test battery, visual suppression and smooth pursuit are of extreme value, as are some auditory tests such as discrimination of interrupted speech and cortical response audiometry using frequency glides as stimuli. Dynamic posturography and magnetic resonance imaging (MRI) have recently proved valuable in the diagnosis. Research is needed concerning the most efficient test battery for early detection of solvent-induced lesions. During further research it is important to unveil other toxic agents, like heavy metals and alcohol, and their damage to the central nervous system and to make comparisons between these substances and the lesions caused by hydrocarbon solvents.

Animals↗

Nuclear export of metazoan replication-dependent histone mRNAs is dependent on RNA length and is mediated by TAP.

Replication-dependent histone mRNAs are the only metazoan mRNAs that are not polyadenylated, ending instead in a conserved stem-loop sequence. Histone pre-mRNAs lack introns and are processed in the nucleus by a single cleavage step, which produces the mature 3' end of the mRNA. We have systematically examined the requirements for the nuclear export of a mouse histone mRNA using the Xenopus oocyte system. Histone mRNAs were efficiently exported when injected as mature mRNAs, demonstrating that the process of 3' end cleavage is not required for export factor binding. Export also does not depend on the stem-loop binding protein (SLBP) since mutations of the stem-loop that prevent SLBP binding and competition with a stem-loop RNA did not affect export. Only the length of the region upstream of the stem-loop, but not its sequence, was important for efficient export. Histone mRNA export was blocked by competition with constitutive transport element (CTE) RNA, indicating that the mRNA export receptor TAP is involved in histone mRNA export. Consistent with this observation, depletion of TAP from Drosophila cells by RNAi resulted in the restriction of mature histone mRNAs to the nucleus.

Active Transport, Cell Nucleus↗

[The effect of bFGF and sucralfate on cell proliferation during continuous tissue expansion].

OBJECTIVE: To investigate the effect of local application of bFGF combined with sucralfate on the cell proliferation during continuous tissue expansion (CTE). METHODS: Nine white pigs were selected to undergo the continuous tissue expansion in this study and treated with bFGF and sucralfate, respectively as the following groups: group 1 with both bFGF and sucralfate, group 2 only with bFGF, group 3 with only sucralfate, and group 4 with saline as control. Fifteen samples were taken in each pig for immunohistochemistry analysis 1-14 days and 6 weeks after the operation. RESULTS: In the group with both bFGF and sucralfate, the epidermic basal cells proliferated significantly after the operation and reached top level in 3 days, which was statistical higher than the control group, but the multiplication of basal cell was the lowest 14 days after the operation, still more than the control group. In dermal layer, proliferation of fibroblasts, vessel endothelial cells, hair follicles epidermic cells and sweat gland epicytes was also significant higher in the group with both bFGF and sucralfate than that the control group and reached top level 7 day after the operation, but the proliferation of cells decreased obviously 14 days after the operation, still higher than the control group. The mitotic activity of cells returned to the basal level in 42 days. There were no significant differences among the group 2, group 3 and group 4. CONCLUSION: Local application of both bFGF and sucralfate could be more effect to induce cells multiplication during early skin expansion to facilitate the growth of neoformed skin soft tissue.

Animals↗

The cytotoxic properties of Serpulina hyodysenteriae.

Examination of colonic enterocytes inoculate with pure culture of S. hyodysenteriae by phase-contrast microscopy revealed that only few spirochaetes adhere to epithelial cells. S. hyodysenteriae was observed to be highly motile, showed corkscrew-like movement which might suggest that bacteria were trying to penetrate and damaged the host cells. The pattern of motility provide evidence of a chemotaxis. Supernatant of S.hyodysenteriae lysate were found to cause CTE in CHO, Vero and PK-15 culture. This support the hypothesis that damage is consistent with the presence of toxin. Inhibition activity of serpulinas hemolysin preparation with streptolysin S inhibitors confirms the suggestion that the mechanism by which S. hyodysenteriae toxin effects the cells seems to be similar to the action of streptococcal toxin S.

Animals↗

[Cytotoxic effect of lymphocytes on peritoneal macrophages of mice in contact dermatitis induced by dinitrochlorbenzene].

Contact dermatitis was induced in BALB/c mice by means of cutaneous application of dinitrochlorbenzol (DNCB) solution. Peritoneal macrophages from DNCB-sensitized and intact mice were cultivated in flat tubes for 48 hours after the 20th day of the experiment, when the DNCB cutaneous test became positive. A suspension of the peripheral lymph node lymphocytes was added to this culture. The lymphocytes fromthe DNCB-sensitized mice had a cytotoxic effect (CTE) on the target cells (peritoneal macrophages) during the co-incubation; the STE was tested with trypane blue in 48 hours. No macrophage lysis was observed in combined incubation of cells from the intact mice.

Animals↗

Regional ventricular enlargement as an in vivo biomarker of cumulative biomechanical neurodegeneration in former American football players.

INTRODUCTION: Repetitive head impacts (RHIs) have been linked to later life neurodegeneration, yet the in vivo structural correlates of cumulative biomechanical loading remain unclear. We examined whether regional ventricular morphology in former American football players reflects exposure burden and traumatic encephalopathy syndrome (TES) classification. METHODS: Participants included 170 male former football players and 54 age-matched asymptomatic male controls from the Diagnostics, Imaging, and Genetics Network for the Objective Study and Evaluation of Chronic Traumatic Encephalopathy Research Project. Subject-specific manual segmentation quantified lateral ventricle, inferior horn, third ventricle, and fourth ventricle volumes. Group and exposure associations were tested using generalized least squares models. RESULTS: Former players showed larger left inferior lateral ventricle volume than controls, with the largest effects among professional players. Greater cumulative linear and rotational acceleration exposure was associated with enlargement across lateral ventricular and inferior horn regions. DISCUSSION: Regional ventricular enlargement may represent an in vivo marker of cumulative biomechanical loading after RHI exposure.

Humans↗

Limbic-predominant age-related TDP-43 encephalopathy (LATE-NC): Co-pathologies and genetic risk factors provide clues about pathogenesis.

Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) is detectable at autopsy in more than one-third of people beyond age 85 years and is robustly associated with dementia independent of other pathologies. Although LATE-NC has a large impact on public health, there remain uncertainties about the underlying biologic mechanisms. Here, we review the literature from human studies that may shed light on pathogenetic mechanisms. It is increasingly clear that certain combinations of pathologic changes tend to coexist in aging brains. Although "pure" LATE-NC is not rare, LATE-NC often coexists in the same brains with Alzheimer disease neuropathologic change, brain arteriolosclerosis, hippocampal sclerosis of aging, and/or age-related tau astrogliopathy (ARTAG). The patterns of pathologic comorbidities provide circumstantial evidence of mechanistic interactions ("synergies") between the pathologies, and also suggest common upstream influences. As to primary mediators of vulnerability to neuropathologic changes, genetics may play key roles. Genes associated with LATE-NC include TMEM106B, GRN, APOE, SORL1, ABCC9, and others. Although the anatomic distribution of TDP-43 pathology defines the condition, important cofactors for LATE-NC may include Tau pathology, endolysosomal pathways, and blood-brain barrier dysfunction. A review of the human phenomenology offers insights into disease-driving mechanisms, and may provide clues for diagnostic and therapeutic targets.

Humans↗