Tau is the pathological protein in several neurodegenerative disorders classified as frontotemporal lobar degeneration (FTLD), including corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP). We report an unusual tauopathy in three Japanese patients presenting with Parkinsonism and motor neuron disease (neuroimaging revealed frontotemporal cerebral atrophy in two patients who were examined). At autopsy, all cases showed FTLD with the most severe neuronal loss and gliosis evident in the premotor and precentral gyri. Although less severe, such changes were also observed in other brain regions, including the basal ganglia and substantia nigra. In the spinal cord, loss of anterior horn cells and degeneration of the corticospinal tract were evident. In addition, the affected regions exhibited neuronal cytoplasmic inclusions resembling neurofibrillary tangles. Immunostaining using antibodies against hyperphosphorylated tau and 4-repeat tau revealed widespread occurrence of neuronal and glial cytoplasmic inclusions in the central nervous system; the astrocytic tau lesions were unique, and different in morphology from astrocytic plaques in CBD, or tufted astrocytes in PSP. However, immunoblotting of frozen brain samples available in two cases revealed predominantly 4R tau, with the approximately 37-kDa and 33-kDa low-molecular mass tau fragments characteristic of CBD and PSP, respectively. No mutations were found in the tau gene in either of the two cases. Based on these clinicopathological, biochemical, and genetic findings, we consider that the present three patients form a distinct 4R tauopathy associated with sporadic FTLD.
Haemophilus parasuis is the causative agent of Glässer's disease, which leads to serious economic loss to the swine industry. Although antibiotics are widely used to control infections, outbreaks of this disease repeatedly happen. In this study, emodin from Polygonum cuspidatum showed potent inhibitory effect against H. parasuis. The minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) values of emodin were 32 and 64μg/mL, respectively. The antibacterial kinetic curves indicated the antibacterial activity of emodin was in a concentration-dependent manner. Cell membrane permeability and flow cytometry assays proved that emodin could destroy cell membrane integrity and increase membrane permeability, and fluorescence spectra assay indicated emodin has influenced conformation of membrane protein. Under transmission electron microscopy, serious lesions of H. parasuis exposed to emodin (64μg/mL) were found, including irregular cell shape, plasmolysis, ruptured cell wall and membrane and cytoplasmic vacuolation. These results suggested that emodin could be used as candidate for treating Glässer's disease.
Bone and intramedullary bacterial infections are one of the most serious complications of the surgical repair of fractures. To reduce the incidence of implant-related infections, several biomaterial surface treatments with integrated antibiotics, antiseptics, or metal ions have been developed for implants. In this study, we evaluated the antibacterial activity and biocompatibility of 317L stainless steel containing 4.5% copper alloy (317L-Cu) in vitro and in vivo using an animal model. Common pathogens of implant-related infections are Staphylococcus aureus and Escherichia coli, which were injected into implant materials to study their antimicrobial potential. We compared antimicrobial potential of 317L-Cu with 317L stainless steel (317L) and titanium (Ti-6Al-4V) alloys as controls. Compared with controls, 317L-Cu materials inhibited colonization by both bacteria in vitro and in vivo. Compared with 317L and Ti-6Al-4V controls, 317L-Cu showed no significant difference in colony formation of osteoblast-like cells on metal surfaces after 72 h of incubation in vitro. Metal screws containing these materials were also made for our vivo study in a rabbit model. Tissue-implants were analyzed for infection and inflammatory changes by hematoxylin-eosin staining of implants in bone. The screw tract inflammation and infection of 317L-Cu was minimal, although some inflammatory cells gathered at acutely infected sites. In addition, after materials had been implanted for 14 days in vivo, the expression of insulin-like growth factor-1 (IGF-1) in osteoblasts around 317L-Cu screws tracts had increased compared with 317L and Ti-6Al-4V controls. Overall, 317L-Cu demonstrated strong antimicrobial activity and biocompatibility in vitro and in vivo and may be used as a biomaterial to reduce implant-related infections.
Based on previous studies about microflora regulation and immunity enhancement activities of polysaccharides from Codonopsis pilosula Nannf. var. modesta (Nannf.) L. T. Shen (CPP), there is little study on intestinal mucosal immunity, which is a possible medium for contacting microflora and immunity. In the present study, the BALB/c mice were divided into five groups (eight mice in each group), including a normal group (Con), a model control group (Model), and model groups that were administered CPP (50, 100, 200 mg/kg/d) orally each day for seven days after intraperitoneal injection of 60 mg/kg BW/d cyclophosphamide (CP) for three days. CPP recovered the spleen index and restored the levels of IFN-γ, IL-2, IL-10, as well as serum IgG. In addition, it elevated ileum secretory immunoglobulin A (sIgA), the number of Lactobacillus and acetic acid content in cecum. These results indicated that CPP plays an important role in the protection against immunosuppression, especially mucosa immune damage, and the inhibition of pathogenic bacteria colonization, which could be considered a potential natural source of immunoregulator.
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