Low Skeletal Muscle Mass Is Associated With Perioperative Neurocognitive Disorder Due To Decreased Neurogenesis in Rats.

BACKGROUND: Perioperative neurocognitive disorder (PND) is a postsurgical complication associated with neuroinflammation and impaired hippocampal neurogenesis, in which brain-derived neurotrophic factor (BDNF) plays a key role. Sarcopenia refers to age-related muscle loss that causes cognitive decline, muscle atrophy, and postoperative delirium. Rats with tail suspension (TS) were used to represent a low-activity model, which involves decreased hind limb function by TS. This hind limb unloading by TS can induce sarcopenia in 2 weeks. However, the relationship between PND and muscle atrophy is unclear. In this experiment, we investigated whether preoperative muscle atrophy induced by TS would affect neurogenesis and accelerate PND in rats. METHODS: Sixty 21-week-old rats were assigned to 4 groups: the TS group, the TS with surgery (TS + S) group, the control group, and the control with surgery (control + S) group. After the abdominal manipulation under 3% sevoflurane anesthesia, cognitive function was assessed using the Morris water maze test and a fear-conditioning test. Neurogenesis was evaluated by checking BDNF secretion and immunohistochemical staining in the hippocampus. RESULTS: The TS + S group showed impaired swimming latency (difference of means = 12.4 versus control + S; 95% confidence interval [CI], 2.0-22.7; P = .016) (difference of means = 15.2 versus TS; 95% CI, 0.4-30.1; P = .043) and path length (difference of means = 147.8 versus control + S; 95% CI, 20.7-274.9; P = .020) in the maze test and cued fear memory (difference of means = -26.0 versus TS; 95% CI, -46.4 to -5.6; P = .006) (difference of means = -22.3 versus control + S; 95% CI, -42.7 to -1.9; P = .026) in the fear-conditioning test. The postoperative levels of BDNF in the TS + S and TS groups were reduced compared with the other groups (P = .002). The number of neural precursors in the dentate gyrus was significantly lower in the TS + S group (P < .001). CONCLUSIONS: We observed that preoperative hind limb muscle atrophy, indicated by TS, was associated with an increased occurrence of PND through the reduction in BDNF and neurogenesis after abdominal surgery in young adult rats. Therefore, we concluded that preoperative low skeletal muscle mass can induce PND due to impaired postoperative neurogenesis. Our findings might indicate that low-cost perioperative interventions, such as preoperative exercise, is beneficial to preventing PND.

Tail suspension is useful as a sarcopenia model in rats.

BACKGROUND: Sarcopenia promotes skeletal muscle atrophy and exhibits a high mortality rate. Its elucidation is of the highest clinical importance, but an animal experimental model remains controversial. In this study, we investigated a simple method for studying sarcopenia in rats. RESULTS: Muscle atrophy was investigated in 24-week-old, male, tail-suspended (TS), Sprague Dawley and spontaneously hypertensive rats (SHR). Age-matched SD rats were used as a control group. The skeletal muscle mass weight, muscle contraction, whole body tension (WBT), cross-sectional area (CSA), and Muscle RING finger-1 (MuRF-1) were assessed. Enzyme-linked immunosorbent assay was used to evaluate the MuRF-1 levels. Two muscles, the extensor digitorum longus and soleus muscles, were selected for representing fast and slow muscles, respectively. All data, except CSA, were analyzed by a one-way analysis of variance, whereas CSA was analyzed using the Kruskal-Wallis test. Muscle mass weight, muscle contraction, WBT, and CSA were significantly lower in the SHR (n = 7) and TS (n = 7) groups than in the control group, whereas MuRF-1 expression was dominant. CONCLUSIONS: TS and SHR presented sarcopenic phenotypes in terms of muscle mass, muscle contraction and CSA. TS is a useful technique for providing muscle mass atrophy and weakness in an experimental model of sarcopenia in rats.

The Effect of Tranexamic Acid Administration on Perioperative Bleeding in Patients Undergoing Knee or Hip Arthroplasty: A Single-Centre Retrospective Study.

OBJECTIVE: Tranexamic acid (TXA) has been used to reduce perioperative bleeding in various surgeries because of its antifibrinolytic effect. Recently, patients undergoing orthopaedic surgery in our institution received a loading dose of TXA (10 00 mg) before surgery, followed by 100 mg h-1 until the end of surgery. The purpose of the present study was to evaluate the efficacy of TXA administration on the perioperative blood loss in patients undergoing knee arthroplasty or hip arthroplasty. METHODS: A retrospective cross-sectional study was conducted for the records in patients who underwent surgery without TXA administration (control group) and patients who underwent surgery with TXA administration (TXA group). Amount of intraoperative blood loss, intraoperative infusion volume, intraoperative blood transfusion volume, postoperative blood transfusion volume, changes in haemoglobin concentrations (ΔHb) and estimated blood loss were collected. Data were adjusted by propensity score method. RESULTS: A total of 126 (63 in the control group and 63 in the TXA group) patients were included during the study period. Intraoperative infusion, postoperative transfusion, ΔHb and estimated blood loss were significantly reduced in the TXA group, although there were no significant differences in the volumes of intraoperative transfusion and blood loss. CONCLUSION: The administration of TXA (loading dose of 1000 mg and continuous infusion of 100 mg h-1) reduced postoperative transfusion and perioperative blood loss. These results indicated that TXA administration is useful for reducing perioperative blood loss in patients undergoing knee or hip arthroplasty.

IL­1ß and TNF­α suppress TGF­ß­promoted NGF expression in periodontal ligament­derived fibroblasts through inactivation of TGF­ß­induced Smad2/3­ and p38 MAPK­mediated signals.

Mechanosensitive (MS) neurons in the periodontal ligament (PDL) pass information to the trigeminal ganglion when excited by mechanical stimulation of the tooth. During occlusal tooth trauma of PDL tissues, MS neurons are injured, resulting in atrophic neurites and eventual degeneration of MS neurons. Nerve growth factor (NGF), a neurotrophic factor, serves important roles in the regeneration of injured sensory neurons. In the present study, the effect of pro­inflammatory cytokines, including interleukin 1ß (IL­1ß) and tumor necrosis factor α (TNF­α), on transforming growth factor ß1 (TGF­ß1)­induced NGF expression was evaluated in rat PDL­derived SCDC2 cells. It was observed that TGF­ß1 promoted NGF expression via Smad2/3 and p38 mitogen­activated protein kinase (MAPK) activation. IL­1ß and TNF­α suppressed the TGF­ß1­induced activation of Smad2/3 and p38 MAPK, resulting in the abrogation of NGF expression. NGF secreted by TGF­ß1­treated SCDC2 cells promoted neurite extension and the expression of tyrosine hydroxylase, a rate­limiting enzyme in dopamine synthesis in rat pheochromocytoma PC12 cells. These results suggested that pro­inflammatory cytokines suppressed the TGF­ß­mediated expression of NGF in PDL­derived fibroblasts through the inactivation of TGF­ß­induced Smad2/3 and p38 MAPK signaling, possibly resulting in the disturbance of the regeneration of injured PDL neurons.

Water-soluble factors eluated from surface pre-reacted glass-ionomer filler promote osteoblastic differentiation of human mesenchymal stem cells.

Surface pre-reacted glass­ionomer (S­PRG)-containing dental materials, including composite and coating resins have been used for the restoration and/or prevention of dental cavities. S­PRG is known to have the ability to release aluminum, boron, fluorine, silicon, and strontium ions. Aluminum ions are known to be inhibitors whereas boron, fluorine, silicon, and strontium ions are known to be promoters of mineralization, via osteoblasts. However, it remains to be clarified how an aqueous eluate obtained from S­PRG containing these ions affects the ability of mesenchymal stem cells (MSCs), which are known to be present in dental pulp and bone marrow, to differentiate into osteogenic cell types. The present study demonstrated that 200­ to 1,000­fold­diluted aqueous eluates obtained from S­PRG significantly upregulated the mRNA expression level of the osteogenic differentiation marker alkaline phosphatase in human MSCs (hMSCs) without exhibiting the cytotoxic effect. In addition, the 500­ to 1,000­fold­diluted aqueous eluates obtained from S­PRG significantly and clearly promoted mineralization of the extracellular matrix of hMSCs. It was additionally demonstrated that hMSCs cultured on the cured resin composites containing S­PRG fillers exhibited osteogenic differentiation in direct correlation with the weight percent of S­PRG fillers. These results strongly suggested that aqueous eluates of S­PRG fillers promoted hard tissue formation by hMSCs, implicating that resins containing S­PRG may act as a useful biomaterial to cover accidental exposure of dental pulp.

[Efficacy and safety of S-1 plus docetaxel combination therapy for patients with advanced gastric cancer].

Recently, the significant efficacy of S-1 monotherapy or S-1 plus CDDP combination therapy has been reported. Docetaxel also has been reported to have favorable efficacy in gastric cancer. In addition, docetaxel can be administered in outpatient clinics. We investigated the efficacy and safety of S-1 plus docetaxel combination therapy for 35 naive patients with advanced gastric cancer. Docetaxel was administered at a dose of 40 mg/m(2) on day 1, and oral S-1 was administered at the full dose of 80 mg/m(2) twice daily for two weeks followed by one week rest. MST was 300 days, and the response rate was 42. 9%. Although leucopenia was observed in 31%, all patients were able to be continue this therapy. In conclusion, we considered that this S-1 plus docetaxel combination therapy was effective and safe in advanced gastric cancer, and convenient for outpatients.

Brasilicardin A. A Novel Tricyclic Metabolite with Potent Immunosuppressive Activity from Actinomycete Nocardiabrasiliensis.

A novel tricyclic metabolite, brasilicardin A (1), with potent immunosuppressive activity has been isolated from the cultured broth of the actinomycete Nocardia brasiliensis IFM 0406, and the structure including absolute stereochemistry was established on the basis of spectroscopic data, chemical means, and X-ray analysis. Brasilicardin A (1) is the first tricyclic compound consisting of an anti/syn/anti-perhydrophenanthrene skeleton with a rhamnose, an N-acetylglucosamine, and an amino acid moiety.