心房颤动患者心房组织ATP敏感性钾通道基因转录表达的研究

目的 探讨心房颤动患者心房组织ATP敏感性钾通道(Kir6.2)基因转录的变化。方法 35例风湿性心瓣膜病患者,心外科手术时被取右心耳组织。通过逆转录-聚合酶链反应,以三磷酸甘油醛脱氢酶(GAPDH)为内参照,测量心耳组织Kir6.2通道的mRNA表达量。结果 窦性心律组和阵发性房颤组心房组织Kit6.2的mRNA水平均显著高于慢性房颤组(P<0.05);而阵发性房颤组心房组织Kir6.2的mRNA又显著高于窦性心律组(P<0.05)。结论 Kir6.2通道转录水平的改变可能是相应ATP敏感性钾通道产生的内向整流钾电流(IKATP)重构的分子基础,Kir6.2基因转录改变可能是促进房颤发生和持续的因素之一。     

Exposure to Bisphenol AF disrupts sex hormone levels and vitellogenin expression in zebrafish

Bisphenol AF (BPAF) is widely used in food‐contact products, electronic devices, and as a cross‐linking reagent in fluoroelastomers. There are growing concerns about its toxicity and endocrine‐disrupting effects based on its structural similarity with bisphenol A (BPA). The endocrine‐disrupting effects of BPAF were studied by exposing 2‐month‐old zebrafish to 0, 0.05, 0.25, or 1 mg/L BPAF for 28 days and evaluating the effect on growth, histopathology, hormone levels, enzyme activity, and gene expression. The overall fitness was not significantly affected. There were no apparent alterations in the gills and intestine tissues of both sexes after BPAF exposure. However, exposure to 1 mg/L BPAF caused damage to the liver in the male fish, characterized by hepatocellular swelling and vacuolation. There was no obvious effect in the liver of female fish, suggesting that the hepatic toxicity of BPAF is gender dependent. Gonadal examination indicated that exposure to 1 mg/L BPAF caused induction of acellular areas in the testis and retardation of oocyte development in the ovary. BPAF exposure increased free triiodothyronine levels of females in a dose‐dependent manner. In males, the testosterone levels decreased in a concentration‐dependent manner. In contrast, estradiol levels increased in a concentration‐dependent manner and were significantly higher in males exposed to 1 mg/L BPAF compared with the controls. In females, 0.05 and 0.25 mg/L BPAF caused an increase in testosterone levels. Furthermore, the estradiol levels increased in females exposed to 0.05 and 1 mg/L. We observed an upregulation of hepatic vitellogenin in both sexes and significantly higher levels in males exposed to 1 mg/L BPAF and females exposed to 0.25 mg/L BPAF, suggesting that BPAF has an estrogenic activity. Our results indicate that BPAF is an endocrine‐disrupting chemical that exerts reproductive toxicity and estrogenic effects on zebrafish. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 285–294, 2016.     

Prior exposure to acrolein accelerates pulmonary inflammation in influenza A-infected mice

The combustion product acrolein contributes to several smoke-related health disorders, but whether this immunomodulatory toxicant alters pulmonary susceptibility to viruses has received little attention. To study the effects of prior acrolein dosing on the severity of influenza A viral infection, male BALB/c mice received acrolein (1mg/kg) or saline (control) via oropharyngeal aspiration either 4- or 7-days prior to intranasal inoculation with either influenza A/PR/8/34 virus or vehicle. At 0, 2, 4 and 7 days post-inoculation, lung samples were assessed for histological changes while pulmonary inflammation was monitored by estimating immune cell numbers and cytokine levels in bronchoalveolar lavage fluid (BALF). After viral challenge, animals that were exposed to acrolein 4 days previously experienced greater weight loss and exhibited an accelerated inflammatory response at 2 days after viral inoculation. Thus compared to saline-pretreated, virus-challenged controls, BALF recovered from these mice contained higher numbers of macrophages and neutrophils in addition to increased levels of several inflammatory cytokines, including IL-1α, IL-1β, IL-6, TNF, IFN-γ, KC, and MCP-1. The acrolein-induced increase in viral susceptibility was suppressed by the carbonyl scavenger bisulphite. These findings suggest acute acrolein intoxication "primes" the lung to mount an accelerated immune response to inhaled viruses.     

海藻真菌菌株 Aspergillus sp. AF044 中的两个新天然产物

目的：研究海藻真菌 Aspergillus sp. AF044 的化学成分。方法：通过色谱层析柱对提取物进行分离纯化, 并通过波谱解析（一维、二维的核磁共振谱和质谱）确定化合物的结构。结果：分离纯化得到3个化合物, 分别鉴定为6-hydroxy-5-methoxy- 3-methyl-3, 6-dihydro-2H-pyran-4-carboxylic acid （1）, 8, 9-dihydroxy-8, 9-deoxyaspyrone（2） and penicillic acid（3）。结论：化合物 1和 2 是首次发现的新化合物。化合物 3 在多种真菌菌株中分离得到。     

Mechanism of bisphenol AF‐induced progesterone inhibition in human chorionic gonadotrophin‐stimulated mouse Leydig tumor cell line (mLTC‐1) cells

Bisphenol AF (BPAF) has been shown to inhibit testicular steroidogenesis in male rats. However, the precise mechanisms related to the toxic effects of BPAF on reproduction remain poorly understood. In the present study, a mouse Leydig tumor cell line (mLTC‐1) was used as a model to investigate the mechanism of steroidogenic inhibition and to identify the molecular target of BPAF. Levels of progesterone and the concentration of cyclic adenosine monophosphate (cAMP) in cells exposed to BPAF were detected, and expression of key genes and proteins in steroid biosynthesis was assessed. The results showed that BPAF exposure decreased human chorionic gonadotrophin (hCG)‐stimulated progesterone production in a dose‐dependent manner. The 24‐h IC₅₀ (half maximal inhibitory concentration) value for BPAF regarding progesterone production was 70.2 µM. A dramatic decrease in cellular cAMP concentration was also observed. Furthermore, BPAF exposure inhibited expression of genes and proteins involved in cholesterol transport and progesterone biosynthesis. Conversely, the protein levels of steroidogenic acute regulatory protein (StAR) were not altered, and those of progesterone were still decreased upon 22R‐hydroxycholesterol treatment of cells exposed to higher doses of BPAF. Together, these data indicate that BPAF exposure inhibits progesterone secretion in hCG‐stimulated mLTC‐1 cells by reducing expression of scavenger receptor class B type I (SR‐B1) and cytochrome P450 (P450scc) due to the adverse effects of cAMP. However, StAR might not be the molecular target in this process.     

Esmolol versus diltiazem in atrial fibrillation following coronary artery bypass graft surgery

SUMMARY

Purpose: Atrial fibrillation (AF) is the most common arrhythmic complication following coronary artery bypass graft surgery (CABG). The efficacy and safety of esmolol and diltiazem were compared in patients with post-CABG AF.

Methods: This study was a retrospective medical record review of consecutive patients with post-CABG AF >15?min in duration with a ventricular rate >110?b.p.m. who received either i.v. esmolol (n?=?59) or i.v. diltiazem (n?=?48) with or without concomitant digoxin therapy at a single university-affiliated teaching hospital. Treatment success was defined as either cardioversion to sinus rhythm or a reduction in the ventricular rate to <90?b.p.m. at 24?h after the start of therapy. Time to treatment success and the occurrence of adverse effects were considered secondary outcomes.

Results: A total of 107 patients with post-CABG AF were treated with i.v. esmolol (n?=?59) or i.v. diltiazem (n?=?48). The mean maximum dose of esmolol and diltiazem were 115?±?38?μg/kg/min and 11.2?±?3.5?mg/h, respectively. The average duration of the esmolol and diltiazem infusions were 19.3?±?8.5?h and 20.1?±?11.3?h, respectively. Based on the combined efficacy endpoint of cardioversion or ventricular rate control, esmolol was significantly more effective than diltiazem (90% vs 77%; p?=?0.038). Time to treatment success was significantly better for esmolol than diltiazem at all time points (1, 2,4,6,12, and 24?h post-treatment). The overall incidence of adverse effects was 44% with esmolol and 60% with diltiazem (p?=?0.04). Rates of drug discontinuance for adverse effects were significantly less for esmolol (20%) compared with diltiazem (38%) (p?=?0.04).

Conclusions: Esmolol is significantly more effective than diltiazem in the management of post-CABG AF. More patients converted to sinus rhythm with esmolol as compared to diltiazem. Esmolol was associated with fewer adverse effects than diltiazem, including adverse effects leading to drug discontinuance. Due to study design limitations (retrospective data collection), an adequately powered randomised, controlled trial is needed to confirm these preliminary findings.     

老年房颤患者行非心脏手术的麻醉处理体会

目的分析老年房颤患者施行非心脏手术的麻醉处理过程,探讨围手术期的监测手段和治疗措施。方法 28例老年房颤患者中,9例采用全身麻醉,14例采用椎管内阻滞,5例采用臂丛神经阻滞。其中23例患者术前接受抗心律失常药物治疗。结果 28例患者均安全度过围手术期。结论积极处理原发病,改善心功能,选择适当的麻醉方式以及药物,严密监测,及时纠正心律失常以及血流动力学紊乱,尽可能消除加重房颤的诱因,是病人安全度过围术期的重要保证。     

A bioactivity-guided study on the anti-diarrheal activity of Polygonum chinense Linn

Ethnopharmacological relevance

Polygonum chinense Linn., a folk medicine, has long been used for the treatment of diarrhea and enteritis in southwestern China. However, the components responsible for its anti-diarrheal activity are still poorly understood.

Aim of the study

To determine anti-diarrheal activities of Polygonum chinense L. and to identify its active components through bioactivity-guided isolation technique.

Materials and methods

Animals were orally administered with the extract of Polygonum chinense L. The anti-diarrheal effects of 75% ethanol extract, four fractions with different polarities from 75% ethanol extract, different eluates collected from Diaion HP-20 macroporous resin chromatography, ellagic acid and corilagin, were examined based on mouse models of castor oil- and magnesium sulfate-induced diarrhea.

Results

The results showed that the 75% ethanol extract of Polygonum chinense L. exhibited significant anti-diarrheal activities in a dose-dependent manner in two mouse models. Through in vivo bioactivity-guided fractionation processes, n-butanol and aqueous fractions were found to exhibit prominent anti-diarrheal activities, and two major compounds, ellagic acid and corilagin, from these active fractions were found to possess anti-diarrheal effects.

Conclusion

Present study provides evidence of the utilization of Polygonum chinense L. for diarrhea, and ellagic acid and corilagin are two components contributing to the anti-diarrheal effect.     

Immunohistochemical evidence for degeneration of cholinergic neurons in the forebrain of the rat following injection of AF64A-picrylsulfonate into the dorsal hippocampus

The cholinergic neurotoxin, AF64A-picrylsulfonate, was unilaterally infused into the dorsal hippocampus of Wistar rats (2 nmol/2 μl/4 min; A 6.2, L^s 1.5, H 6.5, Paxinos and Watson). After 19 days the animals' brains were processed for immunohistochemical staining of choline acetyltransferase (ChAT). Morphometry and counting of ChAT-immunoreactive profiles revealed shrinkage and disappearance of cholinergic neurons in the medial septum and diagonal band of Broca at the lesioned brain side. These data indicate a retrograde degeneration of cholinergic neurons following injection of AF64-A-picrylsulfonate into the dorsal hippocampus of the rat.