In mice, apolipoprotein A-II (apoA-II) self-associates to form amyloid fibrils (AApoAII) in an age-associated manner. We postulated that the two most important factors in apoA-II amyloidosis are the Apoa2(c) allele, which codes for the amyloidogenic protein APOA2C (Gln5, Ala38) and transmission of amyloid fibrils. To characterize further the contribution of the Apoa2(c) allele to amyloidogenesis and improve detection of amyloidogenic materials, we established transgenic mice that overexpress APOA2C protein under the cytomegalovirus (CMV) immediate early gene (CMV-IE) enhancer/chicken beta promoter. Compared to transgene negative (Tg(-/-)) mice that express apoA-II protein mainly in the liver, mice homozygous (Tg(+/+)) and heterozygous (Tg(+/-)) for the transgene express a high level of apoA-II protein in many tissues. They also have higher plasma concentrations of apoA-II, higher ratios of ApoA-II/apolipoprotein A-I (ApoA-I) and higher concentrations of high-density lipoprotein (HDL) cholesterol. Following injection of AApoAII fibrils into Tg(+/+) mice, amyloid deposition was observed in the testis, liver, kidney, heart, lungs, spleen, tongue, stomach and intestine but not in the brain. In Tg(+/+) mice, but not in Tg(-/-) mice, amyloid deposition was induced by injection of less than 10(-8) mug AApoAII fibrils. Furthermore, deposition in Tg(+/+) mice occurred more rapidly and to a greater extent than in Tg(-/-) mice. These studies indicate that increased levels of APOA2C protein lead to earlier and greater amyloid deposition and enhanced sensitivity to the transmission of amyloid fibrils in transgenic mice. This transgenic mouse model should prove valuable for studies of amyloidosis. 相似文献
Using near infrared spectroscopy and repetitive transcranial magnetic stimulation (rTMS), we studied interhemispheric interactions
between bilateral motor and sensory cortices in humans. RTMS consisted of a triple-pulse burst (50 Hz) repeated every 200 m
for 2 s (10 bursts, 30 pulses); one kind of theta burst TMS (TBS) (Huang et al. in Neuron 45:201–206, 2005). The hemoglobin concentration changes were recorded at the right prefrontal cortex, premotor area (PM), primary hand motor
area (M1) and primary sensory area (S1) during and after TBS over the left PM, M1 and S1 or sham stimulation in eight normal
volunteers. In addition, motor evoked potentials (MEPs) to TMS over the right M1 were recorded from the left first dorsal
interosseous muscle after the conditioning TBS over left S1. TBS over PM induced a significant oxy-Hb decrease at the contralateral
PM. TBS over M1 elicited a significant oxy-Hb decrease at the contralateral S1, and TBS over S1 significant oxy-Hb decreases
at the contralateral M1 and S1. MEPs to TMS of the right M1 were significantly suppressed by the conditioning TBS over the
left S1. These results suggest that there are mainly inhibitory interactions between bilateral PMs and bilateral sensorimotor
cortices in humans. Those are partly compatible with the previous findings. In addition to between the primary motor cortices,
bilateral connection is requisite for smooth bimanual coordination between the sensory cortices or premotor cortices. 相似文献
Sarcopenic dysphagia is characterized by difficulty swallowing due to a loss of whole-body skeletal and swallowing muscle mass and function. However, no study has reported on swallowing muscle mass and quality in patients with sarcopenic dysphagia.
Objective
To compare the differences in swallowing muscle mass and quality between sarcopenic and nonsarcopenic dysphagia.
Method
A cross-sectional study was performed in 55 older patients, who had been recommended to undergo dysphagia assessment and/or rehabilitation. Sarcopenic dysphagia was diagnosed using a diagnostic algorithm for sarcopenic dysphagia. The thickness and area of tongue muscle and geniohyoid muscle (coronal plane and sagittal plane), and the echo-intensity of the tongue and geniohyoid muscles were examined by ultrasound.
Results
The study participants included 31 males and 24 females (mean age of 82 ± 7 years), with 14 having possible sarcopenic dysphagia, 22 probable sarcopenic dysphagia, and 19 without sarcopenic dysphagia. The group with sarcopenic dysphagia had a significantly lower cross-sectional area and area of brightness of the tongue muscle than that observed in the group without sarcopenic dysphagia. The most specific factor for identifying the presence of sarcopenic dysphagia was tongue muscle area (sensitivity, 0.389; specificity, 0.947; cut-off value, 1536.0), while the factor with the highest sensitivity was geniohyoid muscle area brightness in sagittal sections (sensitivity, 0.806; specificity, 0.632; cut-off value, 20.1). Multivariate logistic regression analysis showed that the area of the tongue muscle and its area of brightness were independent risk factors for sarcopenic dysphagia. However, geniohyoid sagittal muscle area and area of brightness showed no significant independent association with sarcopenic dysphagia.
Conclusion
Tongue muscle mass in patients with sarcopenic dysphagia was smaller than that in patients without the condition. Sarcopenic dysphagia was also associated with increased intensity of the tongue muscle. 相似文献
Objective: Parkinson's disease (PD) is characterized by deterioration of the nigrostriatal system and associated with chronic neuroinflammation. Glial activation has been associated with regulating the survival of dopaminergic neurons and is thought to contribute to PD through the release of proinflammatory and neurotoxic factors, such as reactive nitric oxide (NO) that triggers or exacerbates neurodegeneration in PD. Polyunsaturated fatty acids (PUFAs) exert protective effects, including antiinflammatory, antiapoptotic, and antioxidant activity, and may be promising for delaying or preventing PD by attenuating neuroinflammation and preserving dopaminergic neurons. The present study investigated the effects of fish oil supplementation that was rich in PUFAs on dopaminergic neuron loss, the density of inducible nitric oxide synthase (iNOS)-immunoreactive cells, and microglia and astrocyte reactivity in the substantia nigra pars compacta (SNpc) and striatal dopaminergic fibers.
Methods: The animals were supplemented with fish oil for 50 days and subjected to unilateral intrastriatal 6-hydroxydopamine (6-OHDA)-induced lesions as a model of PD.
Results: Fish oil mitigated the loss of SNpc neurons and nerve terminals in the striatum that was caused by 6-OHDA. This protective effect was associated with reductions of the density of iNOS-immunoreactive cells and microglia and astrocyte reactivity.
Discussion: These results suggest that the antioxidant and antiinflammatory properties of fish oil supplementation are closely related to a decrease in dopaminergic damage that is caused by the 6-OHDA model of PD. 相似文献
This study evaluated the effect of chlorhexidine/thymol (CHX/T) and fluoride (F) varnishes on biofilm formation in vitro. Hydroxyapatite discs coated with varnish were first immersed in saline for 0, 3, 7 or 14 d, then immersed in pasteurized saliva. The discs were incubated for 20 h with a bacterial suspension containing Actinomyces naeslundii, Fusobacterium nucleatum, Streptococcus oralis, and Veillonella dispar. Uncoated discs were used as controls. Growth of bacteria on the discs was evaluated by culture and by scanning electron microscopy (SEM). Bacterial vitality was examined by fluorescence staining. In the CHX/T-treated group, bacterial accumulation was delayed, and the total number of bacteria was significantly lower than in the controls. In the F-treated group, the total number of bacteria did not differ from the control, although the number of S. oralis was lower. Bacterial vitality in the CHX/T and F groups did not differ from that in the controls. The total number of bacteria on the CHX/T-treated discs immersed in saline was significantly higher than that on the non-immersed discs. Biofilm development was inhibited by the CHX/T varnish but not by the F varnish. The effect of the CHX/T varnish decreased following the immersion of discs in saline. 相似文献
The sigma-1 receptor (Sig-1R) can bind psychostimulants and was shown to be up-regulated in the brain of methamphetamine self-administering rats. Up-regulation of Sig-1Rs has been implicated in neuroplasticity. However, the mechanism(s) whereby Sig-1Rs are up-regulated by psychostimulants is unknown. Here, we employed a neuroblastoma cell line B-104, devoid of dopamine receptors and transporter, and examined the effects of psychostimulants as well as cAMP on the expression of Sig-1Rs in this cell line, with a specific goal to identify signal transduction pathway(s) that may regulate Sig-1R expression. Chronic treatments of B-104 cells with physiological concentrations of cocaine or methamphetamine failed to alter the expression of Sig-1Rs. N6,2'-O-Dibutyryl-cAMP (dB-cAMP), when used at 0.5 mM, caused a down-regulation of Sig-1Rs that could be blocked by a protein kinase A (PKA) inhibitor, N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride (H-89). However, dB-cAMP, when used at 2 mM, caused an up-regulation of Sig-1Rs that was insensitive to the H-89 blockade but was partially blocked by an extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase inhibitor PD98059 (2'-amino-3'-methoxyflavone). Furthermore, 2 mM dB-cAMP induced an ERK phosphorylation lasting at least 90 min, at which time the phosphorylation caused by 0.5 mM dB-cAMP had already diminished. PD98059, applied 90 min after addition of 2 mM dB-cAMP, attenuated the Sig-1R up-regulation. Our results indicate that cAMP is bimodal in regulating Sig-1R expression: a down-regulation via PKA and an up-regulation via ERK. Results also suggest that psychostimulants may manipulate the cAMP-PKA-Sig-1R and/or the cAMP-ERK-Sig-1R pathways to achieve a neuroplasticity that favors addictive behaviors. 相似文献