Effect of etodolac on the prostaglandin concentrations in the kidney of the normal rat

The effect of acute and subchronic dosing with etodolac on the renal PGE₂ and 6-keto-PGF_1α concentrations in the normal rat were studied. Etodolac and other nonsteroidal antiinflammatory drugs (NSAIDs) were administered orally, at equieffective antiinflammatory doses, to normal rats either as a single dose or as seven daily doses. Whole kidney prostaglandin (PG) concentrations were measured. In the acute study, etodolac (3 mg/kg) did not significantly lower the PGE₂ levels for up to 4 hr postdosing. In contrast, naproxen (3 mg/kg) and piroxicam (0.5 mg/kg) significantly decreased the PGE₂ levels to about 20% and 60% of control, respectively. Similar reductions in 6-keto-PGF_1α concentrations were observed. In the subchronic study, etodolac (3 mg/kg/day) did not lower either PGF₂ or 6-keto-PGF_1α concentrations whereas naproxen (3 mg/kg/day), piroxicam (0.5 mg/kg/day), indomethacin (1 mg/kg/day), and aspirin (300 mg/kg/day) significantlydecreased both PGs. In both studies, the effect of etodolac was significantly different from that of the NSAIDs. It is concluded that etodolac possesses only a very weak capacity to lower renal PGs, and therefore is unlikely to cause any renal complications related to PG biosynthesis inhibition.     

Actions of ethnobotanically selected Cree anti-diabetic plants on human cytochrome P450 isoforms and flavin-containing monooxygenase 3

Aim of the study

Cree traditional medicine is commonly used concomitantly with prescribed drugs to treat health problems related to type II diabetes (T2D) that is endemic in the Cree population. However, the safety of traditional Cree medicines with respect to drug metabolism is unknown.

Materials and methods

Seventeen anti-diabetic plant extracts were screened for their potential inhibition of 11 isoforms of the drug-metabolizing cytochrome P450s (CYPs), and flavin-containing monooxygenase 3 (FMO3) in fluorometric plate reader assays. Comparative analyses were conducted to determine if particular extracts were more inhibitory, or if particular enzymes were more inhibited.

Results

Many anti-diabetic plant extracts inhibited the CYPs, with CYP2C and 3A isoforms being most prone to inhibition. The order of inhibition for the enzymes by the Cree plant extracts was: 2C19 > 3A7 > 3A5 > 3A4 > 2C9 > 2C8 > FMO3 > 1A2 > 2E1 > 19 > 2D6 > 2B6. Extracts from Rhododendron groenlandicum, Sorbus decora, and Kalmia angustifolia were identified as having strong inhibition towards many CYP isoforms.

Conclusion

These findings demonstrate that extracts from most plant species examined have the potential to affect CYP2C- and 3A4-mediated metabolism, and have the potential to affect the bioavailability and pharmacokinetics of conventional and traditional medicines during concomitant use.     

氧化苦参碱对人胃癌SGC-7901细胞株生长的影响

目的观察氧化苦参碱对人胃癌SGC-7901细胞株体外增殖率的影响情况。方法噻唑蓝（MTT）比色测定法确定氧化苦参碱对胃癌SGC-7901细胞存活抑制作用。结果试验浓度下氧化苦参碱对SGC-7901细胞增殖抑制作用呈剂量依赖性，当浓度为12mg／ml时，对SGC-7901增殖的抑制率最大，达到87．63％。结论氧化苦参碱对人胃癌SGC-7901细胞的增殖具有明显的抑制作用。     

明胶降解物对大鼠真皮成纤维细胞增殖及Ⅰ型胶原蛋白分泌的影响

目的 探讨组织工程心瓣膜常用人工基质材料--明胶发生降解后的产物对大鼠真皮成纤维细胞增殖及Ⅰ型胶原蛋白分泌的影响. 方法 利用酶组合技术制备明胶降解物（gelatin hydrolysate, GH）,采用超滤的方法分离出低分子量明胶降解物组分（gelatin hydrolysate fraction, GHF）,用于5只SD大鼠真皮成纤维细胞的体外培养.采用CCK-8活细胞计数试剂盒（Cell Counting Kit-8）检测细胞的增殖情况,ELISA试剂盒检测细胞I型胶原蛋白的分泌情况. 结果 ①GHF对细胞增殖作用的浓度效应：在0.125～1.0 mg/ml浓度范围内,GHF对细胞的促增殖作用呈现先增强后减弱的趋势,在0.25 mg/ml时,细胞增殖率最大,达到（47.54±16.35）%;②GH与GHF对细胞增殖影响比较：GH与GHF均具有促进细胞增殖的作用,且在浓度为0.25 mg/ml时,促细胞增殖作用无显著差异[（27.04±15.21）% vs （39.22±15.55）%, P=0.177];③GH与GHF对细胞分泌Ⅰ型胶原蛋白影响比较：GHF组第3天时Ⅰ型胶原分泌量为（28.06±5.60）pg/105,与空白对照的（18.24±4.52）pg/105相比,有显著差异（P=0.006）,而GH组直至第6天时Ⅰ型胶原蛋白分泌量,与空白对照相比,无统计学意义（P=0.103）. 结论 分子量大小不同的明胶降解物GH与GHF均具有促进大鼠真皮成纤维细胞增殖的作用,且分子量较小的GHF还具有促进细胞I型胶原分泌的功能.     

Bizarre parosteal osteochondromatous proliferation (Nora’s lesion): report of two cases

Abstract We describe two cases of bizarre parosteal ostechondromatous proliferation (BPOP), commonly known as Nora’s lesion from the author who first described it, arising from the hands of two middle-aged patients. We emphasize the rarity of this lesion and the difficulty in diagnosis, since the histological pattern may mimic that of a malignant sarcoma.     

Liver regeneration in acute severe liver impairment: a clinicopathological correlation study.

BACKGROUND: Although normally quiescent, the adult mammalian liver possesses a great capacity to regenerate after different types of injury. Major players in the regeneration process are mature residual cells, including hepatocytes, cholangiocytes and stromal cells. However, if the regenerative capacity of mature cells is impaired, hepatic progenitor cells (HPCs) are activated and expand into the liver parenchyma. Upon transit amplification, the progenitor cells generate new hepatocytes and biliary cells to restore liver homeostasis. AIMS/METHODS: To study the relationship between different histopathological parameters as well as their correlations with clinical parameters and outcome, we examined liver specimens from 74 patients with acute or subacute severe liver impairment by immunohistochemistry for CK7/CK19 (evaluation of HPCs activation/differentiation), Mib1(Ki 67)/P21 (evaluation of proliferative activity/proliferation arrest of hepatocytes) and hematoxylin and eosin (evaluation of hepatocyte loss). RESULTS: Of the 74 patients, 32% survived without transplantation, 14% died without transplantation and 54% were transplanted. Our results show that a threshold of 50% loss of hepatocytes, associated with significant decrease in the proliferative activity of remaining mature hepatocytes, is needed for extensive hepatic progenitor cell activation. Such activation is a sign of disease severity and occurs early (within 1 week) in the disease course. However, development of intermediate hepatocytes, suggesting HPCs differentiation towards mature hepatocytes, takes at least 1 week's time. We found a positive correlation between histopathological parameters (percentage hepatocyte loss, number of proliferating hepatocytes and number of HPCs) and clinical parameters of liver impairment such as model for end stage liver diseases (MELD). Surviving patients compared with those who either died or were transplanted had significantly less hepatocyte loss, less HPCs activation and more mature hepatocyte proliferative activity. Hepatocyte proliferative activity and degree of hepatocyte loss were the most important independent histopathological parameters in predicting outcome. CONCLUSION: Liver biopsy can provide important additional information in a patient with severe acute liver impairment.     

氯胺酮对体外培养大鼠神经干细胞增殖与凋亡的影响

目的探讨氯胺酮对体外培养夫鼠神经干细胞(NSC)增殖与凋亡的影响。方法采用无血清培养和单细胞克隆技术,在大鼠海马分离培养具有单细胞克隆能力的细胞群,采用免疫荧光细胞化学技术证实为NSC。将NSC以5×10~4/孔接种于96孔培养板中,分别加入浓度为0(未加氯胺酮)、5、10、20、50、100、200、500、1000 mmol·L~(-1)氯胺酮,每个浓度5孔。采用四甲基偶氮唑蓝比色法检测NSC光密度(OD),并计算生长抑制率(RI)。采用流式细胞仪测定氯胺酮浓度为0、10、100、500、1000 mmol·L~(-1)时NSC凋亡率。结果与氯胺酮浓度0时比较,200、500、1000 mmol/L氯胺酮可降低NSC OD,升高RI,10、100、500、1000 mmol·L~(-1)氯胺酮可升高NSC凋亡率(P＜0．05或0．01)。结论氯胺酮对体外培养大鼠NSC增殖有抑制作用,并能诱导NSC凋亡,且该作用与氯胺酮浓度有关     

103Pd放射性核素支架抑制损伤血管平滑肌细胞增殖的实验研究

[目的]采用兔腹主动脉损伤致再狭窄的动物模型,探讨钯-103(103Pd)放射性核素支架对损伤血管中膜平滑肌细胞增殖的影响。[方法]选用雄性新西兰兔50只,随机分为普通支架组及核素支架组,设正常对照。分别于术后3、7、14、28及56 d取材,进行病理形态学、透射电镜、免疫组化(增殖细胞核抗原PCNA、细胞周期素蛋白Cy-clin E)及原位杂交(C-myc mRNA)实验观察。[结果]①光镜下发现,核素支架组管腔狭窄程度明显低于普通支架组,术后第56天最显著(P<0.01);②透射电镜显示,术后3~28 d,核素支架组中膜血管平滑肌细胞增殖明显低于普通支架组,7d时达峰,为13.78％±0.64％vs19.53％±0.44％(P<0.01);③免疫组化显示,术后3~28 d核素支架组PCNA及Cyclin E表达均低于普通支架组,7 d为表达高峰,PCNA为16.35％±0.79％vs24.36±0.55％,Cy-clin E为14.78％±1.07％ vs 22.65％±1.00％(P<0.01)。④对c-myc mRNA进行原位杂交显示,术后3~28 d核素支架组的表达明显低于普通支架组,7 d达峰值,为17.48％±0.53％ vs 25.34％±0.87％(P<0.01);⑤C-mycmRNA与PCNA相关性分析提示二者呈明显正相关(P<0.01)。[结论]103Pd放射性核素支架通过抑制损伤血管中膜平滑肌细胞的增殖,降低再狭窄的程度,从而减少再狭窄的发生率。     

丁酸对人结肠癌细胞株SW1116增殖及分化状态的影响

目的:探讨结肠中膳食纤维的酵解产物丁酸对人结肠癌细胞株生长、增殖及分化状态的影响。方法:将传代人结肠癌SW1116细胞株接种于不含及合不同浓度(2、3、4、7、10 mmol/L)丁酸的培养基中。经6、24、48和72h后,用四唑蓝(MTT)法测定细胞增殖率、细胞匀浆中癌胚抗原(CEA)及和碱性磷酸酶(ALP)的表达;同时用电镜观察细胞形态的改变。结果:丁酸对SW1116细胞株的生长抑制作用呈浓度依赖性,在所观察的丁酸浓度及时限内,最高抑制率达53.9％。同时丁酸能大大增加SW1116细胞CEA和ALP的表达;当丁酸浓度≥7mmol/L和培养时间≥48h时,二者增加最为显著(P<0.001)。电镜显示丁酸能使细胞表面微绒毛明显增多。结论:丁酸能抑制SW1116细胞株的生长并诱导其分化。     

XGD-1对人外周血T淋巴细胞增殖和IL-2R表达的影响

目的 探讨XGD—l的免疫抑制作用及其作用机理。方法 不同浓度的XGD—l作用于植物血凝索(PHA)和刀豆索A(ConA)诱导的正常人外周血T淋巴细胞，共同培养48h和72h，用改良MTT法观察XGD—l对人T淋巴细胞增殖的影响，用流式细胞术检测XGD—l对T淋巴细胞表面IL—2R表达的影响；同时观察联合应用CsA和XGD—l对细胞增殖及IL—2R表达的影响。结果 XGD—l对PHA和ConA诱导的正常人外周血T淋巴细胞增殖有明显的抑制作用，其作用与药物浓度有关，在一定剂量范围内，抑制作用随XGD—l剂量的递增而加强；XGD—l对PHA和ConA激活的T淋巴细胞表面IL-2R的表达有显著抑制作用，阳性率从正常对照活化细胞的47．67％降为25．03％；联合应用CsA，上述抑制作用增强。结论 XGD-l具有免疫抑制作用，能降低IL-2R表达，可能是其免疫抑制作用的重要机理之一。