Trans-suppression of defense DEFB1 gene in intestinal epithelial cells following Cryptosporidium parvum infection is associated with host delivery of parasite Cdg7_FLc_1000 RNA

Parasitology Research - To counteract host immunity, Cryptosporidium parvum has evolved multiple strategies to suppress host antimicrobial defense. One such strategy is to reduce the production of...     

家蝇幼虫抗茵肽粗提物对人肝癌HepG2细胞凋亡、钙离子浓度及线粒体膜电位变化的影响

本文从肿瘤细胞凋亡及作用机制的角度出发初步探讨了家蝇幼虫抗菌肽粗提物对人肝癌HepG2细胞的影响.采用Hoechst 33258荧光染色法在荧光显微镜下观察家蝇抗菌肽对HepG2细胞形态学的影响.并通过流式细胞术分别观察家蝇抗菌肽粗提物对HepG2细胞凋亡、钙离子浓度及线粒体膜电位变化的影响.Hoechst 33258荧光染色法结果显示家蝇抗菌肽粗提物作用于HepG2细胞48h后能够引起细胞核发生核凝聚、染色质趋边化、核碎裂等凋亡形态学的改变;流式细胞仪检测结果显示家蝇抗菌肽粗提物能够诱导HepG2细胞发生凋亡、线粒体膜电位下降、细胞内钙离子浓度增加的现象.因此,我们推测家蝇抗菌肽可能通过增加HepG2细胞内钙离子,降低线粒体膜电位,进而诱导细胞凋亡的发生.     

Study comparing the efficacy and renal safety for patients with diabetes switching from dapagliflozin to empagliflozin

Background Previously, dapagliflozin was limited to patients with an estimated glomerular filtration rate (eGFR)?≥?60 mL/min/1.73 m², while empagliflozin can be used for those with an eGFR?≥?45 mL/min/1.73 m². Therefore dapagliflozin was switched to empagliflozin in many patients when eGFR decreased. However, the clinical efficacy and safety of these switcfhes are not clear. Objective In this study, we compared the efficacy and renal safety between patients switching from dapagliflozin to empagliflozin in patients. Setting This is a retrospective study of adult patients (aged?≥?20 years) who had attended the Kaohsiung Medical University Hospital. Method This retrospective observational study included patients who were switched from dapagliflozin to empagliflozin. To assess the effect of other hypoglycemic drugs on efficacy, the types and dose alterations of other hypoglycemic drugs were classified on the defined daily dose (DDD). Main outcome measure The primary outcome measure was the change in hemoglobin A1c (HbA1c) level after 6 months. Patients with HbA1c levels at or lower than the baseline value after 6 months were defined as effective and patients with levels higher than the baseline were defined as invalid. Safety was evaluated by comparing the difference of eGFR between the baseline value and 6 months after treatment. Results Overall, 111 patients were enrolled in the study. Six months after switching from dapagliflozin to empagliflozin, HbA1c significantly reduced, with no statistically significant difference observed in eGFR. In our study, 78 patients were assigned to the effective group (70.3%) and 33 patients were invalid (29.7%). When the other hypoglycemic drugs were grouped by total dosage, fasting plasma glucose and HbA1c only decreased significantly in the "DDD decrease" and "DDD increase" groups. Conclusion Our study showed that switching from dapagliflozin to empagliflozin in patients with type 2 diabetes was effective for blood glucose maintenance and caused no significant changes in renal function. In addition, compared to similar sodium-glucose co-transporter-2 inhibitors, other hypoglycemic drugs may be factors that influence the efficacy of sugar-lowering treatments.

     

Inhibitory action of methadone and its metabolites on erg-mediated K+ current in GH₃ pituitary tumor cells

Methadone (Mtd) is a widely used opioid drug associated with the side effect of hyperprolactinemia. The mechanism of how Mtd induces prolactin secretion remains unclear. The effects of Mtd and its two main metabolites (EDDP: (±)-2-ethyl-1,5-dimethyl-3,3-diphenylpyrrolinium percholarate and EMDP: 2-ethyl-5-methyl-3,3-dipnehyl-1-pyrroline) on ion currents were investigated in GH? pituitary tumor cells. Hyperpolarization-elicited K+ currents in GH? cells bathed in a high-K(+), Ca(2+)-free solution were studied to evaluate the effects of Mtd and other related compounds on the ether-à-go-go-related-gene (erg) K(+) current (I(K(erg))). Mtd suppressed the amplitude of I(K(erg)) in a concentration-dependent manner with an IC(50) value of 10.4 μM. With the aid of a minimal binding scheme, the inhibitory action of Mtd on I(K(erg)) was estimated with a dissociation constant of 8.2 μM. Mtd tended to increase the rate of I(K(erg)) deactivation in a voltage-dependent fashion. EDDP (10 μM) had no effect on I(K(erg)), while EMDP (10μM) slightly suppressed it. In GH? cells incubated with naloxone (30 μM), the Mtd-induced inhibition of I(K(erg)) remained unaltered. Under cell-attached voltage-clamp recordings, Mtd increased the frequency of spontaneous action currents with no change in current amplitude. Similarly, Mtd can suppress I(K(erg)) in differentiated NG108-15 cells; dynorphin A(1-13) did not reverse Mtd-induced inhibition of I(K(erg)). This study shows that Mtd has a depressant effect on I(K(erg)), and suggests its ability to affect membrane excitability and prolactin secretion. The cyclization of Mtd, in which EDDP and EMDP are formed, tends to be critical in removal of the Mtd binding to erg K+ channel.     

Antioxidant and antiplatelet effects of dang-gui-shao-yao-san on human blood cells

Dang-Gui-Shao-Yao-San (DGSYS) is a mixture of medicinal herbs, which has long been used in traditional Chinese medicine for treating anemia and ovulary disorders. Its preparation comprises Angelicae sinensis (Oliv.) Diels, Ligustucum chuanxiong Hort, Paeonia lactiflora pall, Poria cocos (Schw.) Wolf, Atractylodis macrocephala Koidz and Alisma orientalis (Sam.) Juzep. The present study examined the anti-superoxide formation, free radical scavenging and anti-lipid peroxidation activities of DGSYS by xanthine oxidase inhibition, cytochrome C system with superoxide anion released by the fMLP or PMA activating pathway in human neutrophils, and FeCl2 ascorbic acid-induced lipid peroxidation effects on lipids in rat liver homogenate, respectively. DGSYS showed anti-superoxide formation and free radical scavenging activity in a concentration-dependent manner. It also inhibited PMA- but not fMLP-induced superoxide anion released from human neutrophils. These antioxidant actions of DGSYS showed beneficial cytoprotective effects against lipid peroxidation in rat liver homogenate, human platelet aggregation induced by arachidonic acid (AA) and adenosine diphosphate (ADP) and mitomycin C-mediated hemolytic in human erythrocytes.     

曲安奈德与雷珠单抗治疗视网膜静脉阻塞继发黄斑水肿比较

目的： 比较曲安奈德(Triamcinolone Acetonide,TA)与雷珠单抗(Lucentis,LU)治疗视网膜静脉阻塞性黄斑水肿的临床疗效。

方法：回顾性分析40例最佳矫正视力(BCVA,小数视力)≤0.6,黄斑中心凹厚度(CMT)≥250μm的视网膜静脉阻塞性黄斑水肿患者,分别进行玻璃体腔注射TA(22例,4mg,0.1mL)或LU(18例,0.5mg,0.05mL)治疗。比较两种药物治疗前和治疗后1, 2wk; 1, 2, 3,6mo两组CMT与BCVA的改变情况

结果：两组在治疗后视力明显提高,术后各时间点均较术前具有显著改变(P<0.05), TA组治疗后1mo视力最好(BCVA,logMAR=0.30±0.20),LU组治疗后2mo视力最好(BCVA,logMAR=0.21±0.10),两组在治疗后黄斑水肿明显减轻,CMT明显降低,术后各时间点均具有统计学意义(P<0.05),两组治疗后2mo时黄斑水肿程度最低(TA组CMT=274.45±141.81μm,LU组CMT=225.83±22.86μm)。BCVA(小数视力)与CMT呈负相关。各项指标两组间均无统计学差异。

结论： 玻璃体腔注射TA及LU治疗视网膜静脉阻塞性黄斑水肿均可减轻黄斑水肿和改善视力,两者治疗效果无显著差异。     

实验性肝硬化形成过程中肝脏糖胺多糖和胶原含量的变化

采用四氯化碳、高胆固醇饮食等复合致病因子所致肝硬化大鼠模型，检测了肝硬化发生发展过程中肝脏胶原及己糖胺、透明质酸含量的变化。结果表明：随着肝硬化的发生发展肝脏胶原含量呈进行性增加，肝脏透明质酸、己糖胺含量亦相应增加，且在肝脏纤维间隔形成阶段（实验第四、六周）其胶原含量与己糖胺水平呈显著正相关。     

Inhibition of intermediate-conductance Ca2+-activated K+ channel and cytoprotective properties of 4-piperidinomethyl-2-isopropyl-5-methylphenol

The ionic mechanisms and cytoprotective activities of 4-piperidinomethyl-2-isopropyl-5-methylphenol (THPI), an analogue of thymol, were investigated in HL-60 granulocytes and in human erythrocytes, respectively. THPI inhibited K+ outward current (I(K)) in a concentration-dependent manner in HL-60 leukocytes, with an IC50 value of 4 microM. Neither iberiotoxin (200 nM) nor paxilline (1 microM) suppressed the amplitude of I(K), whereas clotrimazole (5 microM) significantly inhibited it. In the inside-out configuration of single channel recordings, application of THPI (5 microM) into the bath medium did not alter the single-channel conductance of intermediate-conductance Ca2+-activated K+ (IK(Ca)) channels (i.e K(Ca)3.1 channels), but it suppressed the channel activity significantly. THPI-induced inhibition of IK(Ca) channels was reversed by a further application of 1-ethyl-2-benzimidazolinone (10 microM). THPI-induced reduction in IK(Ca)-channel activity in these cells was primarily due to a decrease in mean open time. These results provide direct evidence that THPI is capable of suppressing the activity of IK(Ca) channels in HL-60 cells. The antioxidant action of THPI also revealed a beneficial cytoprotective effect against mitomycin C-mediated haemolytic effect in human erythrocytes. The results of this study suggest that blockade of IK(Ca) channels and the membrane-protecting activity of THPI would combine to have beneficial effects in lessening the severity of haemolytic crisis and reducing anaemia in sickle cell disease.     

1545例剖宫产指征分析及干预措施探讨

目的通过分析剖宫产指征,探讨降低剖低宫产率的措施。方法对1999～2003年宁海县的剖宫产率进行统计,并根据2003年的分娩资料统计剖宫产的手术指征。结果5年间宁海县剖宫率从49．14％～64．35％不等;2003年1545例剖宫产中,手术指征依次为难产61．10％、社会因素183．38％、产科并发症18．06％、妊合并症1．29％和其他1．17％。结论引起剖宫产率持续增高的原因较为复杂。因该从多方面着手降低剖宫产率,以保障母婴健康。     

Effects of 4-piperidinomethyl-2-isopropyl-5-methylphenol on oxidative stress and calcium current

4-Piperidinomethyl-2-isopropyl-5-methylphenol (THPI) was synthesized by reaction of thymol with piperidine and formaldehyde. The biological effect of THPI on superoxide anion scavenging activity, antiplatelet activity and calcium current inhibition were investigated. THPI (50 microM) was shown to be a scavenger of superoxide radicals in human neutrophils stimulated with N-formyl-Met-Leu-Phe (66% inhibition). Since superoxide anions are essential for platelet aggregation and L-type Ca2+-channel activity, we further found that THPI inhibited platelet aggregation induced by arachidonic acid (IC50 46.80+/-6.88 microM). The effect of THPI on Ca2+ current in NG108-15 cells was investigated using the whole-cell voltage-clamp technique. THPI inhibited voltage-dependent L-type Ca2+ current (ICa, L). The IC50 value of THPI-induced inhibition of ICa, L was 3.60+/-0.81 microM. THPI caused no change in the overall shape of the current-voltage relationship of ICa, L. This indicates that THPI is an inhibitor of ICa, L in NG108-15 cells. Therefore, the channel-blocking properties of THPI may contribute to the underlying mechanism by which it affects neuronal or neuroendocrine function. Furthermore, no significant cytotoxic effects of THPI (0.3-50 microM) were observed in NG108-15 cells. The results indicate that THPI is a potential reactive oxygen species scavenger and may prevent platelet aggregation or inhibit L-type Ca2+-channel activity, possibly by scavenging reactive oxygen species.