Effects of Lower Past-Year Serum Sodium and Hyponatremia on Depression Symptoms and Cognitive Impairments in Patients With Hemodialysis.

The relationship between hyponatremia, depression symptoms, and cognitive impairments in patients receiving hemodialysis treatment remain unclear. This study aimed to examine the impact of past-year average serum sodium levels on current depression symptoms and cognitive impairments in patients receiving hemodialysis, with adjustment for possible confounders. A total of 200 participants were recruited for this study. Depression symptoms and cognitive impairments were assessed using the Patient Health Questionnaire and Perceived Deficits Questionnaire-5, respectively. Additionally, sociodemographic features, physical health, metabolic factors, and substance use information were collected. Significant associations between serum sodium levels, depression symptoms, and cognitive impairments were found after multivariate regression analysis. Furthermore, such differences were observed profoundly in moderate to profound hyponatremia. Our study revealed exclusive relationships between hyponatremia, depression symptoms, and cognitive impairments. As such, programs of cognitive rehabilitation and emotional regulation should be included in the prevention of chronic kidney disease for moderate to profound hyponatremia.

A prospective randomized study comparing transnasal and peroral 5-mm ultrathin endoscopy.

BACKGROUND/PURPOSE: Differences in patient tolerance, acceptance, and satisfaction of esophagogastroduodenoscopy (EGD) between transnasal (TN) and peroral (PO) routes using a 5-mm video endoscope. METHODS: A total of 220 enrolled patients were assigned randomly to two groups undergoing EGD-110 patients each for TN and PO. The successful rate, procedure time, and adverse events were recorded. After the procedure, patients answered a validated questionnaire of tolerance, acceptance, and satisfaction. RESULTS: There were 6 failures (5.7%) of nasal intubation and two nasal bleeding (2%) among 105 TN-EGD procedures. All PO patients (n=102) completed EGD successfully without adverse event. Compared to PO, the procedure of TN achieved lower successful rate (94% vs. 100%, p=0.01), was complicated with epistaxis (2% vs. 0%) and took longer (mean ± SD 19.9 ± 6.1 min vs. 16.8 ± 6.4 min, p=0.0001). The patients undergoing TN-EGD indicated less discomfort during passing pharynx (scores of 2.1 ± 2.0 vs. 3.1 ± 2.6, p=0.011) but more pain during inserting scope (scores of 2.2 ± 1.6 vs. 1.5 ± 1.8, p=0.0001). Eventually, there were no significant differences between TN and PO regarding the overall procedure discomfort (scores of 10.7 ± 6.6 vs. 11.1 ± 7.8 scores, p=0.9), satisfaction (scores of 41.2 ± 4.2 vs. 41.3 ± 4.6, p=0.91), and acceptability (87.8% vs. 94.2%, p=0.91). CONCLUSION: PO intubation seems an excellent alternative method when using a 5-mm ultrathin endoscopy because it achieves comparable patient tolerance, acceptance, and satisfaction as TN intubation, takes less time and causes lower intubation failure and epistaxis.

Unsedated transnasal percutaneous endoscopic gastrostomy carried out by a single physician.

AIM: The present prospective observational study investigates the safety of transnasal percutaneous endoscopic gastrostomy (T-PEG) carried out by a single physician using an ultrathin endoscope. METHODS: A single endoscopist attempted the unsedated transnasal insertion of a 20-Fr PEG tube using a pull-method in 31 dysphagic patients: 11 females and 20 males aged 76.5±10.6(46-96)years, using a 5-mm-diameter endoscope. The indications for PEG, cardiopulmonary function before and after T-PEG, operation time, success or failure, and any immediate adverse events that occurred during each procedure were recorded. Complications, including peristomal infection, systemic infection, tube lifespan, and patient mortality were monitored throughout the post-T-PEG follow-up period. RESULTS: Thirty (96.8%) of the transnasal PEG insertions were successful. The mean operation time was 14.7±2.9 (10-20) min, and cardiopulmonary function did not change before and after T-PEG. Complications included three (10%) cases of epistaxis, eight (26.6%) cases of minor Pseudomonas wound infection and two cases of Foley-related urinary tract infection (UTI). No self-extubation was observed, and the mean lifespan of the PEG tubes was 10.7±2.2months. Four patients died from pneumonia 10months after T-PEG insertion. CONCLUSION: Unsedated T-PEG insertion carried out by a single physician is a feasible and safe procedure. No major complications or mortality were observed following the procedures; only minor Pseudomonas aeruginosa wound infections were noted. It is an alternative method for dysphagic patients when transoral insertion of endoscopy is impossible.

Combination of Aß clearance and neurotrophic factors as a potential treatment for Alzheimer's disease.

There is no effective drug to treat Alzheimer's disease (AD), a neurodegenerative disease affecting an estimated 30 million people around the world. Strongly supported by preclinical and clinical studies, amyloid-beta (Aß) may be a target for developing drugs against AD. Meanwhile, the fact that localized neuronal death/loss and synaptic impairment occur in AD should also be considered. Neuronal regeneration, which does not occur normally in the mammalian central nervous system, can be promoted by neurotrophic factors (NTFs). Evidence from clinical trials has shown that both Aß clearance and NTFs are potentially effective in treating AD, thus a new approach combining Aß clearance and administration of NTFs may be an effective therapeutic strategy.

Daphnetin prevents chronic unpredictable stress-induced cognitive deficits.

Chronic exposure to stress hormones might impair cognitive functions such as learning and memory, which were associated with many mood disorders and neurodegenerative diseases. In this study, we aimed to screen for effective compounds to prevent cognitive deficits induced by chronic stress. Daphnetin was found to protect the cortical neurons against dexamethasone-induced reduction of cell viability in a dose-dependent manner in vitro. We further evaluated its effects on chronic unpredictable stress (CUS) mice in vivo. Two and 8 mg/kg administration of daphnetin could improve the performance of stress mice in Morris water maze tests and forced swimming tests. The results suggested that daphnetin might be a potent compound to treat cognitive deficits induced by CUS.

Phosphorylation of Akt is involved in protocatechuic acid-induced neurotrophic activity.

OBJECTIVE: To investigate the mechanisms underlying protocatechuic acid (PCA)-induced neurotrophic effects on cultured cortical neurons. METHODS: The mRNA expression of microtubule-associated protein 2 (MAP2) and brain-derived neurotrophic factor (BDNF) were measured by real-time quantitative PCR (qPCR). Subsequently, antagonists were used to study the signaling pathways activated by PCA and western blotting was used to detect the phosphorylation level of kinase-related protein. RESULTS: The mRNA expression of MAP2 and BDNF were upregulated in neurons treated with PCA compared with vehicle control. PCA-induced neurite outgrowth and neuronal survival in cultured cortical neurons were significantly inhibited by ZM241385 (an A(2A) receptor antagonist) and LY294002 (a PI3K inhibitor), but not by K252a (a TrkA receptor antagonist), GÖ6976 (a protein kinase C inhibitor) and PD98059 (a MEK inhibitor). PCA enhanced the phosphorylation of Akt, which could be blocked by LY294002. CONCLUSION: The PI3K/Akt signaling pathway might play an important role in the neurotrophic activity of PCA.

Neurotrophic effects of magnesium fructose 1, 6-diphosphate on cortical neurons.

In this study, we evaluated the neurotrophic effects of magnesium fructose 1, 6-diphosphate (FDP-Mg) on cortical neurons. The results demonstrated that FDP-Mg promoted dendrite outgrowth and neuronal survival in a dose-dependent manner. In order to investigate the associated mechanisms, we determined adenosine triphosphate (ATP) levels and brain-derived neurotrophic factor (BDNF) mRNA expression in cortical neurons. Treatment with FDP-Mg significantly increased ATP levels and BDNF mRNA expression in cortical neurons. These data suggest that FDP-Mg can exert neurotrophic effects on cortical neurons. The increases in BDNF mRNA expression and cellular ATP levels are involved in the neurotrophic effects produced by FDP-Mg.

Nogo-66 receptor activation inhibits neurite outgrowth and increases ß-amyloid protein secretion of cortical neurons.

A Nogo-A to Nogo-66 receptor (NgR) pathway is well known to contribute to the inhibition of the neurite regeneration of adult central nervous system neurons after traumatic injuries. Recent evidence suggests that Nogo-A and NgR are involved in the pathology of Alzheimer's disease (AD), as evidenced by the fact that Nogo-A is overexpressed by hippocampal neurons in patients with AD and is associated with ß-amyloid protein (Aß) deposits in senile plaques. In the present experiments, we investigated the potential role of Nogo-A in both neurite outgrowth and Aß generation in cortical neurons. Our results showed that activation of NgR not only inhibited neurite outgrowth in cortical neurons by activating the rho-associated coiled coil-containing protein kinase (ROCK) and protein kinase C, but also promoted their Aß secretion, which was at least in part activated by ROCK. These findings suggest that the overexpression of Nogo-A and the activation of NgR inhibit neurite outgrowth and alter neuronal metabolism, resulting in overproduction and/or release of Aß, which in turn may trigger the onset and development of AD. Inhibition of ROCK can promote neurite outgrowth and reduce Aß production of cortical neuron, which suggests that ROCK appears to be a good target for AD therapy.

[Neurotrophic effects of protocatechuic acid on neurite outgrowth and survival in cultured cerebral cortical neurons of newborn rat].

OBJECTIVE: To study the neurotrophic effects of protocatechuic acid on neurite outgrowth and survival in cultured cerebral cortical neurons. METHODS: The newborn rat cerebral cortex neurons were cultured in vitro. The convert phase microscope was used to count the survival neurons with neurites and measure the average length of neurites. MTT and LDH assay were carried out to investigate the effect of PCA on the neuronal viability. RESULTS: Compared with control group, different concentration of PCA could increase the number of survival neurons with neurites and the average length of neurites. MTT and LDH assay showed that PCA promoted neuron survival in a dose-dependent manner. CONCLUSION: PCA can enhance the survival of rat cortical neurons with neurites and promote the neurite outgrowth of rat cortical neurons.

[Effects of ferulic acid on bFGF-treated PC12 cells].

OBJECTIVE: To explore the effect and mechanism of ferulic acid on differentiation in bFGF-treated PC12 cells. METHODS: The length of neurite outgrowth and the percentage of PC12 cells induced in the presence of 0 ng/mL or 1 ng/mL bFGF were assayed. RESULTS: Compared with that of control group,ferulic acid could enhance the differentiation effect of bFGF (1 ng/mL) in PC12 cells (P < 0.01) and the enhancing effect could be blocked by the specific MAPK kinase inhibitor, PD98059. CONCLUSION: Ferulic acid potentiates neurite outgrowth in bFGF-treated PC12 cells by MAPK-dependent signaling pathway.

Combined administration of D-galactose and aluminium induces Alzheimer-like lesions in brain.

OBJECTIVE: It has been reported that D-galactose (D-gal) can model subacute aging, and aluminum (Al) acts as a neurotoxin, but combined effects of them have not been reported. The present work aimed to reveal the effect of combined administration of D-gal and Al in mice and compare the effect of D-gal treatment with that of Al treatment. METHODS: Al was intragastrically administered and D-gal was subcutaneously injected into Kunming mice for 10 consecutive weeks. Learning and memory, cholinergic systems, as well as protein levels of amyloid ß (Aß) and hyperphosphorylated tau were determined using Morri water maze test, biochemical assays and immunohistochemical staining, respectively. RESULTS: The mice with combined treatment had obvious learning and memory deficits, and showed decreases in brain acetylcholine (ACh) level and in activities of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE). Formation of senile plaque (SP)-like and neurofibrillary tangle (NFT)-like structures was also observed. The behavioral and pathological changes persisted for at least 6 weeks after withdrawal of D-gal and Al. CONCLUSION: Combined use of D-gal and Al is an effective way to establish the non-transgenic Alzheimer's disease (AD) animal model, and is useful for studies of AD pathogenesis and therapeutic evaluation.

Screening of treatment targets for Alzheimer's disease from the molecular mechanisms of impairment by ß-amyloid aggregation and tau hyperphosphorylation.

ß-Amyloid (Aß) over-expression and tau hyperphosphorylation are considered to be the central events in the pathogenesis of Alzheimer's disease (AD). Studies on them may help elucidate the precise molecular pathogenesis of AD. Until now, although tau protein and Aß remain the foci of AD research, the etiopathogenesis of AD and effective drugs for AD treatment are still largely unsolved. The present review was mainly focused on the molecular mechanism of Aß aggregation-related impairment and the pathways leading to tau hyperphosphorylation, based on which some promising therapeutic targets for AD were also proposed.