川芎嗪治疗重症急性胰腺炎的实验研究

目的探讨川芎嗪对大鼠重症急性胰腺炎的治疗作用及其机制。方法 30只SD大鼠随机分为假手术组、重症急性胰腺炎组(胰腺炎组)和川芎嗪治疗组(治疗组),每组10只。以L-精氨酸注射法制作大鼠重症急性胰腺炎模型,治疗组大鼠在制模成功后给予川芎嗪治疗,在实验后24 h采集标本,比较不同组大鼠胰腺组织HE染色结果,血清淀粉酶、白介素-6(IL-6)、TNF-α水平及胰腺湿/干比率。结果胰腺炎组和治疗组大鼠血清淀粉酶、IL-6和TNF-α水平均显著高于假手术组,差异有统计学意义(P<0.05),治疗组大鼠血清淀粉酶[(883.75±143.25)U/L vs.(1 031.94±146.59)U/L]、IL-6[(148.65±18.94)pg/L vs.(185.79±17.49)pg/L]和TNF-α[(109.31±123.65)pg/mL vs.(155.79±17.49)pg/mL]均低于胰腺炎组,差异有统计学意义(P<0.05)。治疗组大鼠胰腺湿/干比率(9.8±0.7)低于胰腺炎组(12.5±0.8),差异有统计学意义。结论川芎嗪可通过降低重症急性胰腺炎大鼠的血清淀粉酶、IL-6和TNF-α水平发挥治疗作用。     

Reflection on design and testing of pancreatic alpha-amylase inhibitors: an in silico comparison between rat and rabbit enzyme models

Background

Inhibitors of pancreatic alpha-amylase are potential drugs to treat diabetes and obesity. In order to find compounds that would be effective amylase inhibitors, in vitro and in vivo models are usually used. The accuracy of models is limited, but these tools are nonetheless valuable. In vitro models could be used in large screenings involving thousands of chemicals that are tested to find potential lead compounds. In vivo models are still used as preliminary mean of testing compounds behavior in the whole organism. In the case of alpha-amylase inhibitors, both rats and rabbits could be chosen as in vivo models. The question was which animal could present more accuracy with regard to its pancreatic alpha-amylase.

Results

As there is no crystal structure of these enzymes, a molecular modeling study was done in order to compare the rabbit and rat enzymes with the human one. The overall result is that rabbit enzyme could probably be a better choice in this regard, but in the case of large ligands, which could make putative interactions with the −4 subsite of pancreatic alpha-amylase, interpretation of results should be made cautiously.

Conclusion

Molecular modeling tools could be used to choose the most suitable model enzyme that would help to identify new enzyme inhibitors. In the case of alpha-amylase, three-dimensional structures of animal enzymes show differences with the human one which should be taken into account when testing potential new drugs.     

高脂血症性急性胰腺炎36例临床分析

目的 探讨高脂血症性急性胰腺炎的临床特点和发病机制,加强对该病的认识.方法 回顾性分析36例高脂血症性急性胰腺炎(hyperlipidemic acute pancreatitis,HLAP)和同期40例急性胆源性胰腺炎(acute biliary pancreatitis,ABP)患者的临床资料,对其临床特点、实验室指标、治疗方法进行总结.结果 HLAP组中血淀粉酶正常者2例,尿淀粉酶正常者5例,其余患者血尿淀粉酶均不同程度升高;血脂明显高于ABP组(P＜0.05);其并发症及复发率均高于ABP组(P＜0.05).结论 对于高度怀疑胰腺炎者,在入院后开始治疗前应常规查血脂、血尿淀粉酶、腹部CT或彩超,结合临床症状可帮助诊断.除常规治疗外,尽快将血脂降至安全水平是治疗的关键.     

In vivo and in vitro antidiabetic effect of Cistus laurifolius L. and detection of major phenolic compounds by UPLC–TOF-MS analysis

Ethnopharmacological relevance

In Turkish folk medicine, various parts of Cistus laurifolius L. are used to treat gastric ulcer and various types of pains. Additionally the tea prepared from the leaves is used to decrease symptoms of diabetes.

Materials and methods

In the present study, the hypoglycemic effects of aqueous and ethanol extracts of Cistus laurifolius were investigated in normal, glucose loaded hyperglycemic and streptozocin (STZ)-induced diabetic rats. α-Glucosidase and α-amylase enzyme inhibitory effects were determined to evaluate the mechanism of action. Total phenolic content of the extracts were determined by using Folin–Ciocalteu reagent and Ultra Performance Liquid Chromatography–Time of Flight Mass Spectrometer (UPLC–TOF-MS) was used to detect the major phenolic compounds in the extract.

Results

Results indicated that blood glucose levels of the STZ-induced diabetic rats were decreased by ethanol extract at of 250 and 500 mg/kg doses as compared to control group (16%–34%). In glucose loaded animals, extracts have shown a weak hypoglycemic effect (11%–20%). Additionally, the ethanol extract of Cistus laurifolius is found to be a potent inhibitor of α-glucosidase and α-amylase, possibly due to several polyphenolic compounds present within the extract. Twelve major flavonoids (apigenin, quercetin, kaempferol, naringenin, quercitrin and their derivatives), gallic, ellagic and chlorogenic acid in chromatographic fingerprint were analyzed by the on-line UPLC–TOF-MS system.

Conclusions

Due to having inhibitory effect on blood glucose level and carbohydrate digesting enzymes (α-glucosidase and α-amylase), Cistus laurifolius leaves might be beneficial for diabetic patients.     

尿淀粉酶/尿肌酐及尿胰蛋白酶原-2诊断急性胰腺炎的评价

目的探讨尿淀粉酶/尿肌酐(Uamy/Ucr)及尿胰蛋白酶原2测定对急性胰腺炎的临床诊断价值。方法对79例急性胰腺炎患者、48例非胰腺炎急腹症患者和50例健康对照组人员进行血清淀粉酶(Samy)、尿淀粉酶(Uamy)、尿肌酐(Ucr)及尿胰蛋白酶原2测定。结果急性胰腺炎尿胰蛋白酶原2的诊断特异性最高,其特异性和敏感性分别为97.92%和91.14%,其次Uamy/Ucr特异性为91.67%,敏感性为92.41%(临界值为75U/mmol),而临床常用的诊断指标Samy、Uamy的特异性和敏感性均低于前两者。结论尿淀粉酶/尿肌酐比值及尿胰蛋白酶原2检测是较好的早期诊断急性胰腺炎的指标。     

强肌健力方及黄芪多糖对脾虚大鼠胃肠激素水平的影响

目的 观察强肌健力方及其有效组分黄芪多糖对脾虚大鼠血清淀粉酶(AMS)、胃泌素(Gas)和血浆胃动素(MTL)水平变化的影响,探讨强肌健力方防治脾虚证的作用机理.方法 将雄性SD大鼠随机分为正常对照组、脾虚模型组、强肌健力组、黄芪多糖组、强肌健力方去黄芪加黄芪多糖组(简称强肌多糖组),除正常对照组灌服蒸馏水外,其余各组采用大黄复制脾虚模型,分别给予强肌健力方、黄芪多糖、强肌多糖药液灌胃,连续15d.第16天从眼球眶下静脉采血,放射免疫分析法测定Gas和MTL的含量,比色法检测AMS的含量.结果 脾虚模型组大鼠血清AMS、Gas和血浆MTL含量均比正常对照显著降低(P均＜0.01);而强肌健力和强肌多糖组能使大鼠血清AMS、Gas和血浆MTL含量显著升高,与脾虚模型组比较有统计学差异(P均＜0.01),但黄芪多糖组对其影响不明显.结论 强肌健力方能改善和促进消化道机能及胃肠动力学,其作用机理与调节Gas和MTL分泌水平有关.但黄芪多糖对Gas和MTL分泌没有调节作用,需与方中其他药物联合应用方能显效.     

血清总淀粉酶诊断急性胰腺炎96例临床分析

目的：对96例临床急腹症患者,采取静脉血测定血清总淀粉酶活力,以探讨血清总淀粉酶在急性胰腺炎的的意义。方法：计算血清总淀粉酶测定对急性胰腺炎诊断的敏感度、特异度及准确度。结果;血清总淀粉酶对急性胰腺炎诊断的敏感度、特异度及准确度分别为90．91％、80．77％、85．42％。结论：血清总淀粉酶测定对急性胰腺炎早期诊断具很大价值,可以在临床上广泛推广应用。     

Early dual drainage combining transpapillary endotherapy and percutaneous catheter drainage in patients with pancreatic fistula associated with severe acute pancreatitis

BackgroundThe development of pancreatic fistula (PF) associated with pancreatic necrosis is of great concern in the management of severe acute pancreatitis (SAP). We expected that early recognition and intervention of PF combined with percutaneous catheter drainage (PCD) for pancreatic infection may improve SAP outcomes.MethodsFifteen consecutive patients with SAP were enrolled. Whenever feasible, fine-needle aspiration for fluid collection was performed to determine infection and amylase concentration. For infection and PF with amylase-rich fluid, PCD and transpapillary endotherapy (preferably naso-pancreatic drainage) were carried out as soon as possible. PCD was intensively managed by irrigating the sized-up and multiple large bore catheters.ResultsInfected fluid collection and PF were both detected in 13 (86.7%) patients. Pancreatic duct (PD) disruption (n = 6) and organ failure (n = 5) occurred exclusively in patients with amylase-rich collection ≥10,000 U/L. The median timing of PCD and endotherapy was 15.5 and 16.5 days, respectively. No serious complications or mortality resulted from intervention procedures other than stent occlusion in one (6.7%) patient. Surgical intervention due to uncontrollable infection and visceral organ injury was avoided. Fistula closure was achieved in 12 (92.3%) of 13 PF patients with a median duration of 45 days. Disease-related mortality occurred in one (6.7%) patient.ConclusionAmylase-rich fluid collection ≥10,000 U/L may be an indication for further endoscopic investigation of PD disruption. Early dual drainage combining pancreatic endotherapy and PCD is feasible and safe, and may improve treatment outcome.     

Modulatory effects of l-carnitine plus l-acetyl-carnitine on neuroendocrine control of hypothalamic functions in functional hypothalamic amenorrhea (FHA)

Functional hypothalamic amenorrhea (FHA) is a relatively frequent disease due to the combination of metabolic, physical, or psychological stressors. It is characterized by the low endogenous GnRH-induced gonadotropin secretion, thus triggering the ovarian blockade and a hypoestrogenic condition. Up to now various therapeutical strategies have been proposed, both using hormonal treatment as well as neuroactive compounds. Since carnitine, namely l-acetyl-carnitine (LAC), has been demonstrated to be effective in the modulation of the central hypothalamic control of GnRH secretion, we aimed to evaluate whether a combined integrative treatment for 12?weeks of LAC (250?mg/die) and l-carnitine (500?mg/die) was effective in improving the endocrine and metabolic pathways in a group of patients (n?=?27) with FHA. After the treatment, interval mean LH plasma levels increased while those of cortisol and amylase decreased significantly. When patients were subdivided according to baseline LH levels, only hypo-LH patients showed the significant increase of LH plasma levels and the significant decrease of both cortisol and amylase plasma levels. The increased 17OHP/cortisol ratio, as index of the adrenal activity, demonstrated the reduced stress-induced adrenal activity. In conclusion, our data sustain the hypothesis that the integrative administration of LAC plus l-carnitine reduced both the metabolic and the neuroendocrine impairment of patients with FHA.     

Ultrastructural and biochemical analysis of the effects of alendronate on salivary glands of young rats

IntroductionThe bisphosphonates are drugs known by their antiresorptive potency and are widely prescribed for treating and preventing osteoporosis. In the past years the employment of this class of drugs had spread to other pathologies, and it is being prescribed to patients in a wide range of ages. Some adverse effects of bisphosphonate treatment have been highlighted recently, however, little is known about its potential side effects in salivary glands.MethodsNewborn rats received daily doses of 2.5 mg/kg/day of sodium alendronate during 30 days. On the thirtieth day the animals were stimulated with pilocarpine and their parotid and submandibular glands were collected, fixed and embedded for histological and ultrastructural analysis. Some glands were collected for analysis of protein content and amylase activity.ResultsAt light microscopy, the alendronate-treated animals presented an accumulation of secretion granules in their cytoplasm, which was confirmed by the ultrastructural examination. Biochemical analysis revealed an increase in total protein content and decreased amylase levels of both glands in the alendronate-treated animals in relation to the control.ConclusionBased on the current findings, alendronate is probably interfering in secretory pathways of parotid and submandibular glands.