通过前房相关免疫偏离阻止实验性自身免疫前葡萄膜炎

目的 实验性自身免疫性前葡萄膜炎（ＥＡＡＵ）是研究人前葡萄膜炎的有用模型。本研究旨在观察前房相关免疫偏离（ＡＣＡＩＤ）能否阻止ＥＡＡＵ发生。方法 将溶于磷酸盐缓冲液（ＰＢＳ）的牛黑色素蛋白（ＢＭＰ）注射于大鼠右眼前房;对照组动物仅注射ＰＢＳ。７d后使用且加完全福氏佐剂（ＣＦＡ）的ＢＭＰ和百日咳毒素免疫所有动物。通过临床 观察和组织病理学检测葡萄膜炎的严重程度和发病率。通过由注射ＢＭＰ刺激的足垫水肿反     

Prevention of experimental autoimmune anterior uveitis by anterior chamber-associated immune deviation

目的实验性自身免疫性前葡萄膜炎（ＥＡＡＵ）是研究人前葡萄膜炎的有用模型。本研究旨在观察前房相关免疫偏离（ＡＣＡＩＤ）能否阻止ＥＡＡＵ发生。方法将溶于磷酸盐缓冲液（ＰＢＳ）的牛黑色素蛋白（ＢＭＰ）注射于大鼠右眼前房;对照组动物仅注射ＰＢＳ。７ｄ后,使用添加完全福氏佐剂（ＣＦＡ）的ＢＭＰ和百日咳毒素免疫所有动物。通过临床观察和组织病理学检测葡萄膜炎的严重程度和发病率。通过由注射ＢＭＰ刺激的足垫水肿反应评估迟发型超敏反应（ＤＴＨ）。结果与对照组相比,预先眼内注射ＢＭＰ的大鼠,其ＥＡＡＵ的严重程度和发病率减低,且ＤＴＨ反应受到显著抑制。结论这些资料提示ＡＣＡＩＤ可以用来阻止ＥＡＡＵ的发生。     

Inhibition of GABA-gated chloride channels by 12,14-dichlorodehydroabietic acid in mammalian brain

1. 12,14-dichlorodehydroabietic acid (12,14-Cl2DHA) reduced GABA-stimulated uptake of 36Cl- into mouse brain synaptoneurosomes suggesting inhibition of mammalian GABA(A) receptor function. 2. 12,14-Cl2DHA did not affect the binding of [3H]-muscimol to brain membranes but displaced specifically bound [3H]-EBOB. The inhibitory effect on [3H]-EBOB binding was not reversible. 12,14-Cl2DHA reduced the availability of [3H]-EBOB binding sites (Bmax) without changing the KD of the radioligand for remaining sites. 12,14-Cl2DHA did not affect the rate of association of [3H]-EBOB with its chloride channel receptor, but increased the initial rate of [3H]-EBOB dissociation. 3. 12,14-Cl2DHA enhanced the incidence of EPSCs when rapidly applied to cultured rat cortical neurones. Longer exposures produced block of IPSCs with marked increases in the frequency of EPSCs and min EPSCs. 12,14-Cl2DHA also irreversibly suppressed chloride currents evoked by pulses of exogenous GABA in these cells. 4. Ultimately, 12,14-Cl2DHA inhibited all synaptic traffic and action currents in current clamped cells indicating that, in contrast to picrotoxinin (which causes paroxysmal bursting), it is not fully selective for the GABA(A) receptor-chloride channel complex. 5. The depolarizing block seen with 12,14-Cl2DHA in amphotericin-perforated preparations implicates loss of Ca2+ buffering in the polarity change and this may account for inhibition of spontaneous action potentials. 6. Our investigation demonstrates that 12,14-Cl2DHA blocks GABA-dependent chloride entry in mammalian brain and operates as a non-competitive insurmountable GABA(A) antagonist. The mechanism likely involves either irreversible binding of 12,14-Cl2DHA to the trioxabicyclooctane recognition site or a site that is allosterically coupled to it. We cannot exclude, however, the possibility that 12,14-Cl2DHA causes localized proteolysis or more extensive conformational change within a critical subunit of the chloride channel.     

Rapid inhibition of rat brain mitochondrial proton F0F1-ATPase activity by estrogens: comparison with Na+, K+ -ATPase of porcine cortex

Our earlier studies have identified oligomycin sensitivity-conferring protein (OSCP), a subunit of proton F0F1-ATPase/ATP synthase in the mitochondrial inner membranes, as a new estradiol binding protein. This finding suggests that mitochondrial ATPase/ATP synthase could be a potential target for estradiol or compounds with similar structures. Here, we report that estradiol and several other compounds inhibited F0F1-ATPase activity of detergent-solubilized rat brain mitochondrial preparations in a following decreasing order: diethylstilbestrol (half-inhibition concentration, IC50 of 10-25 microM) > alpha-zearalenol, 4-hydroxyestradiol (1C50 of 55 microM) >2-hydroxyestradiol (IC50 of 110 microM), 17beta-estradiol, 17alpha-estradiol > beta-zearalanol > estriol, testosterone, 16alpha-hydroxyestrone > corticosterone, progesterone, dehydroepiandrosterone, dehydroepiandrosterone 3-sulfate, cholesterol (less than 10% inhibition at 140 microM). On the other hand, Na+, K+ -ATPase of porcine cortex showed different sensitivity to the compounds tested above. At 70 microM, the rank of inhibitory potency in decreasing order was as follows: 2-hydroxyestradiol (IC50 of 70 microM) > diethylstilbestrol> 4-hydroxyestradiol > progesterone > alpha-zearalenol, while other compounds had little effect (less than 5%). The data indicate that the ubiquitous mitochondrial F0F1-ATPase is a specific target site for estradiol and related estrogenic compounds; however, under this in vitro condition, the effect seems to require pharmacological concentrations.     

Mechanisms contributing to the deficits in hippocampal synaptic plasticity in mice lacking amyloid precursor protein

Abnormal processing of amyloid precursor protein (APP), in particular the generation of beta-amyloid (Abeta) peptides, has been implicated in the pathogenesis of Alzheimer's disease. This study examined the consequences of deleting the APP gene on hippocampal synaptic plasticity, and upon the biophysical properties of morphologically identified neurones in APP-null mice. The hippocampus of APP-null mice had a characteristic increase in gliosis throughout the CA1 region and a disruption of staining for the dendritic marker MAP2 and the presynaptic marker synaptophysin. The disruption of MAP2 staining was associated with a significant reduction in overall dendritic length and projection depth of biocytin labeled CA1 neurones. In two groups of APP-null mice that were examined at 8-12 months, and 20-24 months of age, there was an impairment in the formation of long-term potentiation (LTP) in the CA1 region compared to isogenic age matched controls. This LTP deficit was not associated with an alteration in the amplitude of EPSPs at low stimulus frequencies (0.033 Hz) or facilitation during a 100 Hz stimulus train, but was associated with a reduction in post-tetanic potentiation. Paired-pulse depression of GABA-mediated inhibitory post-synaptic currents was also attenuated in APP-null mice. These data demonstrate that the impaired synaptic plasticity in APP deficient mice is associated with abnormal neuronal morphology and synaptic function within the hippocampus.     

Hydrogen peroxide induces contraction and raises [Ca2+]i in canine cerebral arterial smooth muscle: participation of cellular signaling pathways

The effects of hydrogen peroxide (H2O2) on isolated canine basilar arteries, and single smooth muscle cells isolated from these arteries, were investigated in the present study. Exposure of isolated endothelium-intact and denuded arterial rings to H2O2, at concentrations of 2.2x10(-5) M to 4.4x10(-3) M, produced concentration-dependent contractile responses. Removal of the endothelium attenuated, but did not eliminate the contractions. H2O2-induced contractions were inhibited, to different degrees, by preincubation of the vessels with low concentrations of staurosporine or bisindolylmaleimide I HCl [antagonists of protein kinase C (PKC)], G?6976 (a PKCalpha and PKCbeta1 selective antagonist), genistein (an antagonist of protein tyrosine kinase), PD-98059 (an antagonist of mitogen-activated protein kinase), wortmannin [an antagonist of phosphatidylinositol 3 (PI3)-kinases], and LY-294002 (an antagonist of PI3-kinases). These agents were also found to relax arteries precontracted by H2O2. Removal of extracellular Ca2+ or pretreatment of the vessels with 5.0 microM verapamil markedly attenuated the contractions. Complete inhibition of the contractile response was obtained after buffering intracellular Ca2+ with BAPTA-AM. A variety of specific pharmacological antagonists of several known vasoconstrictors neither inhibited nor attenuated the H2O2-induced contractions. Exposure of smooth muscle cells to H2O2 (4.4x10(-6) M to 4.4x10(-4) M) significantly raised intracellular Ca2+ ([Ca2+]i) within 20 s. This was abolished in the absence of extracellular Ca2+ or after application of 5.0 microM verapamil. Pretreatment of the cells with low concentrations of staurosporine, bisindolylmaleimide I, G?6976, genistein, PD-98059, wortmannin, and LY-294002 markedly suppressed the H2O2-mediated [Ca2+]i elevation. The present findings suggest that hydrogen peroxide, in vitro, produces endothelium-dependent and independent contractions of canine basilar arteries, which are clearly Ca2+-dependent and are not associated with release of endogenous vasoconstrictors. Several intracellular signal transduction systems, such as PKC (both Ca2+-dependent and Ca2+-independent), protein tyrosine phosphorylation, IP3, mitogen-activated protein kinase and PI3 kinase appear to play a role in the H2O2-induced contractions in cerebral arterial muscle.     

中药材珍珠的X衍射Fourier谱研究

目的：珍珠为常用名贵中药,应用粉未Ｘ衍射Ｆｏｕｒｉｅｒ谱分析,建立各类珍珠的Ｘ衍射特征标记峰,对其进行鉴定。方法：西方应用粉未Ｘ衍射方法对珍珠贝科海水（天然与人工养殖）、淡水珍珠、蚌科三角帆蚌壳、珍珠未与珍珠层粉等９个榈进行了Ｘ衍射Ｆｏｕｒｉｅｒ谱分析计算。结果：海水珍珠、淡水珍珠、珍珠粉与珍珠层粉中的主要成分为珍珠文石型碳酸钙;但后二者中尚含有１０％以下方解石型碳酸钙。同时,获得了有别于文石矿的     

药流与负压吸宫法的效果和可接受性研究

研究的目的:比较RU486/Cytotec药物和负压吸宫术两种流产方法的效果,以及医学的和个人的可接受性.对象为通过咨询,介绍两种流产方法后,让对象自愿选择而组成.年龄在20～34岁.药物组100例,闭经35～42天,第1天口服RU486 600mg,第3天服Cytotec(PGE1)0.4mg,第17、43天回医院随访.手术组100例,闭经≤56天,负压吸宫术后第14、43天回医院随访.结果:完全流产率药物组为89%,手术组为100%.对象选择这两种流产方法的主要原因:药物组94%的人认为痛苦少,手术组的55%认为手术快、节省时间,而且手术同时可取出或放置宫内节育器(占45%).结论:RU486/Cytotec药物流产和负压吸宫术在各自适合的人群中都具有高度的可接受性.两种方法各具优缺点,不能相互取代,二者相辅相成,取长补短,将使终止妊娠的措施更为安全     

Comparison of nifedipine and metoprolol on collateral coronary blood flow in a swine model of chronic coronary obstruction and acute ischaemia during isoflurane anaesthesia

Purpose

This study compared the effects of nifedipine and metoprolol on collateral-dependent myocardial blood flow in a swine model of chronic coronary obstruction and acute ischaemia during isoflurane anaesthesia.

Methods

Collateral coronary circulation was induced in 15 three-week-old piglets by banding of the proximal left anterior descending coronary artery (LAD). After 8–10 wk, the distal LAD was ligcted and the open-chest pigs were randomized to receive infusions of either saline, nifedipine (5 μg·kg^?1 · min^?1) or metoprolol (10 μg · kg^?1 · min^?1) for 30 min during isoflurane anaesthesia (2%). Transient ischaemia was induced by 30 secocclusion of the left circumflex artery. Arterial blood pressures, heart rate and regional myocardial blood flow (radio-labelled microspheres technique) were measured at the end of drug infusion (baseline) and one minute after transient ischaemia.

Results

No differences in the blood flow to the collateral-dependent (CD) myocardium or haemodynamic variables were observed at baseline among the three groups. Following transient ischaemia, in the nifedipine but not in the metoprolol group, blood flow to the CD myocardium was reduced by 28 ± 24% in the epicardium (P< 0.05) and 56 ± 20% in the endocardium (P< 0.01), resulting from intercoronary and transmural steal. This was associated with a moderate increase (10%, P< 0.05) in the heart rate in the nifedipine group.

Conclusions

In a swine model of chronic coronary obstruction and acute ischaemia during isoflurane anaesthesia, the collateral coronary blood flow was maintained in the presence of metoprolol, but reduced in the presence of nifedipine following transient ischaemia due to intercoronary and transmural steal.     

Complications of ultrasound-guided prostate biopsy peripheral zone only versus combined peripheral and transition zone biopsy

The main objectives of this study were to reassess complications associated with transrectal ultrasound-guided biopsies (TRUSBx) of the peripheral zone (PZ) and to compare morbidity of exclusive PZ biopsy to morbidity associated with two additional transition zone (TZ) biopsies. We distributed a self-administered questionnaire assessing TRUSBx complications to 883 consecutive patients who underwent two systematic TZ TRUSBx in addition to systematic sextant PZ TRUSBx, and to 383 consecutive patients who underwent exclusive PZ TRUSBx. Of 316 (35.8%) patients subjects to TZ and PZ TRUSBx, 71% experienced hematuria, 63% hematospermia, 39% rectal bleeding, and 2.2% temperature elevation greater than 38°C. Of 137 (35.8%) patients who exclusively underwent PZ TRUSBx, 57%, 62%, 36%, and 1.4% reported these complications, respectively. Symptom duration and severity were similar in both groups. Although we report a substantially higher incidence of biopsy complications than previously published, these complications are self limited and require no intervention. Furthermore there appears to be no significant difference between complication rates associated with exclusive PZ biopsy compared with those associated with two additional biopsies of the TZ.