Effect of dissolved oxygen in alcoholic beverages and drinking water on alcohol elimination in humans

Oxygen plays an important role in the metabolism of alcohol. An increased dissolved oxygen level in alcoholic beverages reportedly accelerates the elimination of alcohol. Therefore, we evaluated the effect of dissolved oxygen in alcohol and the supportive effect of oxygenated water on alcohol pharmacokinetics after the excessive consumption of alcohol, i.e., 540 ml of 19.5% alcohol (v/v). Fifteen healthy males were included in this randomized, 3 × 3 crossover study. Three combinations were tested: X, normal alcoholic beverage and normal water; Y, oxygenated alcoholic beverage and normal water; Z, oxygenated alcoholic beverage and oxygenated water. Blood alcohol concentrations (BACs) were determined by conversion of breath alcohol concentrations. Four pharmacokinetic parameters (C_max, T_max, K_el, and AUCall) were obtained using non-compartmental analysis and the times to reach 0.05% and 0.03% BAC (T_0.05% and T_0.03%) were compared using one-way analysis of variance (ANOVA) and Duncan's post hoc test. With combination Z, the BAC decreased to 0.05% significantly faster (p < 0.05) than with combination X. Analyzing the pharmacokinetic parameters, the mean K_el was significantly higher for combination Z than for combinations X and Y (p < 0.05), whereas the mean values of C_max, T_max and AUCall did not differ significantly among the combinations. Dissolved oxygen in drinks accelerates the decrease in BAC after consuming a large amount of alcohol. However, the oxygen dissolved in the alcoholic beverage alone did not have a sufficient effect in this case. We postulate that highly oxygenated water augments the effect of oxygen in the alcoholic beverage in alcohol elimination. Therefore, it is necessary to investigate the supportive effect of ingesting additional oxygenated water after heavy drinking of normal alcoholic beverages.     

TL1A blocking ameliorates intestinal fibrosis in the T cell transfer model of chronic colitis in mice

Tumor necrosis factor like cytokine 1A (TL1A) is a member of the TNF superfamily. Accumulating evidence demonstrated the importance of TL1A in the pathogenesis of inflammatory bowel disease (IBD) and suggested a potential role of TL1A blocking in IBD therapy. Here we aimed to explore whether the anti-TL1A antibody could ameliorate intestinal inflammation and fibrosis in IBD. A T cell transfer model of chronic colitis was induced by intraperitoneal injection of CD4⁺CD45RB^high naive T cells isolated from either C57BL/6 wild type (WT) mice or LCK-CD2-Tl1a-GFP transgenic (L-Tg) mice into recombinase activating gene-1-deficient (RAG^?/?) mice. The colitis model mice were treated prophylactically or therapeutically with anti-Tl1a antibody or IgG isotype control. Haematoxylin and eosin staining (H&E staining), Masson's trichrome staining (MT staining) and sirius red staining were used to detect histopathological changes in colonic tissue; immunohistochemical staining was used to detect the expressions of collagen I, collagen III, TIMP1, vimentin, α-SMA and TGF-β1/Smad3. Results showed that anti-Tl1a antibody could reduce intestinal inflammation and fibrosis by inhibiting the activation of intestinal fibroblasts and reducing the collagen synthesis in the T cell transfer model of chronic colitis. The mechanism may be related to the inhibition of TGF-1/Smad3 signaling pathway.     

Nurr-1对小胶质细胞微环境的影响

目的:探讨Nurr-1基因对小胶质细胞活化状态及其微环境的影响。方法:分离培养新生SD大鼠小胶质细胞,纯化、鉴定并分别用脂多糖(LPS)刺激活化和过表达Nurr1基因。实验随机分为小胶质细胞组、Nurr1过表达组、LPS处理组、Nurr1过表达+LPS处理组。ELISA分析过表达Nurr1基因对不同状态小胶质细胞分泌TNF-α、IL-1等炎症相关因子和BDNF、GDNF和PDNF等神经营养因子的影响。结果:(1)小胶质细胞混合培养、纯化、CD11b/c免疫细胞化学鉴定为阳性,纯度在95%;(2)Nurr1基因过表达小胶质细胞转染阳性率90%;(3)ELISA法检测结果显示:过表达Nurr1基因的小胶质细胞显著降低了TNF-α、IL-1的分泌,并促使了BDNF、GDNF和PDNF等神经营养因子的分泌。结论:Nurr1基因可抑制小胶质细胞的活化和减少炎症相关因子的产生,同时可促进GDNF、BDNF、PDNF等与DA能神经元存活和成熟等相关的神经营养因子的分泌。     

A Comparison of Stability and Clinical Outcomes in Single-Radius Versus Multi-Radius Femoral Design for Total Knee Arthroplasty

We compared the intraoperative varus-valgus stability from 0° to 90° of flexion and postoperative clinical outcomes in patients receiving TKA via either a single-radius femoral design (50 TKA, SR group) or multi-radius femoral design (50 TKA, MR group). We measured stabilities at 0°, 30°, 60° and 90° of flexion using a navigation system. The clinical outcomes including HSS scores, WOMAC scores and VAS score during stair climbing were compared after a minimum of 2-year follow-up. The single-radius femoral designs in TKA showed better intra-operative stability at 30° of flexion (7.6 vs. 8.3) compared with the multi-radius femoral design, but not at other angles. However, the clinical outcomes revealed no other significant differences in terms of HSS scores, WOMAC scores and VAS score between two groups.     

(−)-Epigallocatechin-3-gallate inhibits voltage-gated proton currents in BV2 microglial cells

(?)-Epigallocatechin-3-gallate (EGCG), the principal constituent of green tea, protects neurons from toxic insults by suppressing the microglial secretion of neurotoxic inflammatory mediators. Voltage-gated proton channels are expressed in microglia, and are required for NADPH oxidase-dependent reactive oxygen species generation. Brain damage after ischemic stroke is dependent on proton channel activity. Accordingly, we examined whether EGCG could inhibit proton channel function in the murine microglial BV2 cells. EGCG potently inhibited proton currents with an IC₅₀ of 3.7 μM. Other tea catechins, (?)-epigallocatechin, (?)-epicatechin and (?)-epicatechin-3-gallate, were far less potent than EGCG. EGCG did not change the kinetics of proton currents such as the activation and the deactivation time constants, the reversal potential and the activation voltage, suggesting that the gating process of proton channels were not altered by EGCG. EGCG is known to disturb lipid rafts by sequestering cholesterol. However, neither extraction of cholesterol with methyl-β-cyclodextrin or cholesterol supplementation could reverse the EGCG inhibition of proton currents. In addition, the EGCG effect was preserved in the presence of the cytoskeletal stabilizers paclitaxel and phalloidin, phosphatase inhibitors, the antioxidant Trolox, superoxide dismutase or catalase. The proton channel inhibition can be a substantial mechanism for EGCG to suppress microglial activation and subsequent neurotoxic events.     

Momilactone B,an Allelochemical of Rice Hulls,Induces Apoptosis on Human Lymphoma Cells (Jurkat) in a Micromolar Concentration

Although momilactone B has been studied as an allelochemical of rice (Oryza sativa L.), to date we have no report showing the effect of momilactone B on mammalian cells. This study was undertaken to examine whether this allelochemical has anticancer activity on cancer cells. We show here that momilactone B at micromolar doses has antitumor efficacy by inducing apoptosis in several blood cancer cells including human leukemic T cells. In addition, our study elucidated that anticancer activity of momilactone B on human leukemic T cells resulted from the induction of apoptosis via caspase and mitochondria. From these results, momilactone B can be considered as a novel therapeutic strategy for human leukemic T cells from its direct apoptosis-inducing activity.     

后腹腔镜输尿管切开取石治疗嵌顿性输尿管下段结石伴感染的临床体会

目的探讨后腹腔镜输尿管切开取石治疗嵌顿性输尿管下段结石伴有感染的安全性、有效性及实用性。方法回顾性分析2017年6月至2019年6月我科收治的6例诊断为嵌顿性输尿管下段结石伴有感染的病例资料,其中4例术前行体外冲击波碎石术(ESWL)治疗失败,2例术前尿培养阳性且伴有发热,尿常规WBC均为++~+++,均采用后腹腔镜下输尿管下段结石切开取石术,记录其手术时间、术后肠功能恢复时间、总住院天数及相关并发症。结果6例患者行经腹膜后腹腔镜下输尿管下段结石切开取石术均获得成功,无一例中转经腹入路腹腔镜下输尿管切开取石或开放手术。手术时间为55~100 min(平均82.5 min);术后肠功能恢复时间为1~2 d(平均1.7 d),总住院时间7~13 d(平均8.5 d)。其中1例术后拔除尿管后出现腰痛、发热,考虑为前列腺增生、尿潴留、尿液返流所致尿外渗,予保留导尿后症状消失。随访时间3~12个月,均无结石复发、输尿管狭窄等严重并发症。结论经后腹腔入路腹腔镜输尿管下段切开取石术安全可行,创伤小、恢复快,尤其适用于伴感染的输尿管结石患者,值得临床推广,但对术者的腹膜后解剖及腔镜技术提出了更高要求。