重组人表皮生长因子联合氨磷汀治疗鼻咽癌患者放射性口腔黏膜炎的临床观察

目的:观察重组人表皮生长因子外用溶液联合注射用氨磷汀治疗鼻咽癌患者放射性口腔黏膜炎的临床效果。方法:选取2013年8月-2014年8月在我院放疗科接受治疗的96例鼻咽癌患者为研究对象,按随机数字表法分为观察组和对照组各48例。对照组于每次放疗前15~30 min静脉滴注注射用氨磷汀,200 mg/m2,10 min内滴注完毕;观察组在对照组治疗基础上,加用重组人表皮生长因子外用溶液喷洒于口腔黏膜表面。比较两组患者放射性口腔黏膜炎程度、口腔黏膜疼痛程度、NRS2002营养风险评分及营养不良风险率的差异。结果:放疗期间,观察组患者放射性口腔黏膜炎及口腔黏膜疼痛程度均轻于对照组,差异具有统计学意义(P<0.05)。放疗结束后,观察组患者NRS2002营养风险评分及营养不良风险率均低于对照组,差异具有统计学意义(P<0.05)。结论:重组人表皮生长因子联合氨磷汀治疗鼻咽癌放疗患者,可有效降低放射性口腔黏膜炎发生率,减轻口腔黏膜疼痛,减少营养不良风险。     

重组人表皮生长因子联合复方漱口液治疗放射性口腔黏膜炎50例疗效观察

目的：研讨放射性口腔黏膜炎患者合用重组人表皮生长因子与复方漱口液治疗的临床价值。方法87例放射性口腔黏膜炎患者进行分组研究,Ⅰ组37例仅接受复方漱口液含漱,Ⅱ组50例合用重组人表皮生长因子与复方漱口液治疗,评估该两种方案的治疗情况。结果①Ⅱ组接受治疗后的总治疗有效率占96.0％,显著比Ⅰ组的70.3％提高（ P＜0.05）。②Ⅱ组的黏膜愈合时间显著比Ⅰ组的缩短,统计学成立（ P＜0.05）。③治疗前,两组的NRS2002营养风险评测结果经软件分析（P＞0.05）,治疗后,Ⅱ组的评测结果相比Ⅰ组的下降（P＜0.05）。结论合用重组人表皮生长因子与复方漱口液对放射性口腔黏膜炎患者进行治疗,疗效理想,对促进黏膜愈合、预防营养不良均有不错效果,值得推荐。     

白细胞介素-11雾化吸入治疗鼻咽癌同期放化疗导致口腔黏膜炎的疗效观察

目的探讨白细胞介素-11(IL-11)雾化吸入治疗鼻咽癌同期放化疗导致口腔黏膜炎的临床疗效,为鼻咽癌同期放化疗导致口腔黏膜炎的治疗提供新方法。方法选取2010年4月~2013年6月间于我院肿瘤科住院治疗的初诊为鼻咽癌的患者84例,于放疗后2周即药物雾化吸入前,及放疗第3~7周观察口腔黏膜反应变化情况;于放疗结束后1周,观察口腔黏膜反应愈合情况,对比分析IL-11雾化吸入对鼻咽癌同期放化疗导致口腔黏膜炎的治疗效果。结果两组患者放疗后第2周均出现口腔黏膜反应,但观察组患者的口腔黏膜反应分级与对照组相比无显著变化,但随着放射治疗的持续以及放射剂量的增加,观察组患者的口腔黏膜反应分级以Ⅰ~Ⅱ度黏膜反应为主,而对照组患者的口腔黏膜反应分级以Ⅱ~Ⅲ度黏膜反应为主,两组患者组间比较发现,观察组患者的口腔黏膜反应程度较对照组显著增加(P0.05);放疗结束1周后,观察组对于口腔黏膜炎治疗的总有效率为90.5%,与对照组相比显著升高(x2=27.064,P=0.000)。结论IL-11雾化吸入能够有效减轻鼻咽癌同期放化疗导致口腔黏膜反应的程度,对于口腔黏膜炎的治疗具有促进作用。     

表皮生长因子配合口腔护理治疗鼻咽癌放疗后口腔溃疡

目的评价重组人表皮生长因子（rhEGF）配合口腔护理治疗鼻咽癌放疗后口腔溃疡的临床疗效。方法将48例鼻咽癌放疗引起的口腔溃疡患者随机分为对照组和试验组，试验组在常规口腔护理后，使用rhEGF喷于口腔溃疡区域的黏膜，对照组行常规口腔护理。分别观察两组口腔溃疡治疗有效率。结果对照组有效率67％，试验组有效率92％，两组比较差异有统计学意义。结论rhEGF配合口腔护理可以有效治疗鼻咽癌放疗引起的口腔溃疡，方法简便，值得推广。     

重组人表皮生长因子在鼻咽癌放疗中预防放射性口咽炎疗效观察

目的：探讨重组人表皮生长因子在鼻咽癌放疗中预防放射性口咽炎的临床疗效。方法按照随机数字表法将本治疗组收治的64例鼻咽癌患者均分为实验组和对照组,实验组患者在放疗基础上加用重组人表皮生长因子口腔喷雾治疗,对照组患者在放疗基础上加用复方漱口液治疗,比较两组患者放射性口咽炎发生情况以及发生放射性口咽炎时平均放射剂量。结果实验组患者Ⅱ级＋Ⅲ级放射性口咽炎发生率显著低于对照组,差异具有统计学意义（P＜0.05）;实验组患者发生Ⅰ级、Ⅱ级和Ⅲ级放射性口咽炎时平均放射剂量均显著高于对照组,差异具有统计学意义（P＜0.05）。结论重组人表皮生长因子能够有效预防鼻咽癌放疗中放射性口咽炎的发生,提高患者放疗剂量的耐受性,临床疗效显著。     

重组人表皮生长因子凝胶联合复方维生素B12溶液治疗肛周放射性皮炎49例

目的观察重组人表皮生长因子凝胶联合复方维生素B12溶液治疗肛周放射性皮炎的疗效,探讨肛周放射性皮炎治疗的新途径。方法将97例发生放射性皮炎的直肠癌患者分为A组48例和B组49例,两组患者均给予常规护理及换药治疗,B组加用重组人表皮生长因子凝胶及复方维生素B12溶液,进行为期8周的随访,观察两组患者溃疡愈合率及愈合时间。结果B组总有效率为95.92%,平均痊愈时间为(8.2±3.7)d;A组总有效率为83.33%,平均痊愈时间为(16.3±5.2)d。两组比较差异均有统计学意义(P<0.05)。结论重组人表皮生长因子凝胶联合复方维生素B12溶液可有效缩短肛周放射性皮炎溃疡的愈合时间,并增加其愈合率。     

阿拓莫兰治疗头颈部肿瘤放疗所致急性口腔黏膜炎的临床观察

目的观察阿拓莫兰治疗头颈部放疗所致急性口腔黏膜炎的临床效果。方法选择于我科行头颈部放疗的头颈部肿瘤患者98例,均经病理学诊断为头颈部恶性肿瘤。患者随机分为治疗组和对照组,两组采用的放疗技术和剂量基本一致。治疗组:当患者黏膜炎Ⅱ级时,开始给予静脉滴注阿拓莫兰治疗至放疗结束。对照组:当患者黏膜炎Ⅱ级时,开始给予静脉滴注0.9%生理盐水至放疗结束。结果对口腔黏膜炎治疗前,两组患者口腔黏膜炎评定结果比较,无明显差异,无统计学意义(P>0.05)。放疗结束后,对两组患者口腔黏膜炎情况进行调查比较,结果显示,治疗组患者口腔黏膜炎的评定结果明显好于对照组,差异显著,有统计学意义(P<0.05)。结论阿拓莫兰对于治疗头颈部放疗所致急性口腔黏膜炎有一定效果,值得临床使用。     

西帕依固龈液防治口腔黏膜急性放射损伤的疗效观察

目的探讨西帕依固龈液防治放疗患者口腔黏膜急性放射损伤的疗效。方法将80例鼻咽癌、口腔癌术后放疗出现口腔黏膜急性放射损伤的患者随机分成两组,以西帕依固龈液含漱治疗的患者为治疗组,洗必泰液含漱治疗的患者作为对照组,按WHO放射性口腔黏膜反应标准记录患者口腔黏膜放射损伤的程度。结果西帕依固龈液治疗40例,出现Ⅰ、Ⅱ、Ⅲ、Ⅳ级口腔黏膜炎分别为17、14、4、5例;对照组40例,出现Ⅰ、Ⅱ、Ⅲ、Ⅳ级口腔黏膜炎分别为2、5、20、13例;两组比较差异具有显著性（P〈0.05）。结论西帕依固龈液防治口腔黏膜急性放射损伤具有良好的疗效。     

重组人干扰素对鼻咽癌患者放疗后口腔黏膜反应的作用效果分析

目的:研究分析重组人干扰素对鼻咽癌患者放疗后口腔黏膜反应的作用效果.方法:将86例化疗后出现口腔黏膜反应的鼻咽癌患者随机分成两组,各43例.对照组给予常规治疗,试验组在此基础上加用重组人干扰素治疗.观察并对比两组治疗效果以及口腔黏膜修复时间.结果:试验组治疗总有效率为83.72%,明显高于对照组的55.81%;Ⅱ级及以上口腔黏膜平均修复时间明显短于对照组,差异均存在统计学意义(P<0.05).结论:重组人干扰素对鼻咽癌患者放疗后口腔黏膜反应的治疗效果显著,能缩短黏膜修复时间,值得临床推广.     

“新净界”口腔消毒喷雾剂对放射性口腔黏膜炎的防治效果观察

目的:通过实验观察"新净界口腔消毒喷雾剂"对放射性口腔黏膜炎的预防效果。实验方法:选择我2018年1月-10月66例鼻咽癌患者,随机分为两组进行对照实验。实验组为33例,从放疗开始使用新界净口腔消毒喷雾剂;对照组33例,在放疗过程中使用普通漱口液。3级口腔黏膜炎视为终结指标,发生者给予其他药物治疗。结果,两组患者的性别、年龄、放射技术和剂量无明显差异。通过放疗后,两组患口腔黏膜炎人数的对比数据,分析得出结论:"新净界"口腔消毒喷雾剂能延缓放射性口腔黏膜炎的发生时间。     

Interaction of estrone and estradiol with DNA and protein of liver and kidney in rat and hamster in vivo and in vitro

[6,7-³H] Estrone (E) and [6,7-³H]estradiol-17 (E₂) have been synthesized by reduction of 6-dehydroestrone and 6-dehydroestradiol with tritium gas. Tritiated E and E₂ were administered by oral gavage to female rats and to male and female hamsters on a dose level of about 300 g/kg (54 mCi/kg). After 8 h, the liver was excised from the rats; liver and kidneys were taken from the hamsters. DNA was purified either directly from an organ homogenate or via chromatin. The radioactivity in the DNA was expressed in the units of the Covalent Binding Index, CBI = (mol chemical bound per mol DNA-P)/(mmol chemical administered per kg b.w.). Rat liver DNA isolated via chromatin exhibited the very low values of 0.08 and 0.09 for E and E₂, respectively. The respective figures in hamster liver were 0.08 and 0.11 in females and 0.21 and 0.18 in the males. DNA isolated from the kidney revealed a detectable radioactivity only in the female, with values of 0.03 and 0.05 for E and E₂, respectively. The values for male hamster kidney were < 0.01 for both hormones. The minute radioactivity detectable in the DNA samples does not represent covalent binding to DNA, however, as indicated by two sets of control experiments. (A) Analysis by HPLC of the nucleosides prepared by enzyme digest of liver DNA isolated directly or via chromatin did not reveal any consistent peak which could have been attributed to a nucleoside-steroid adduct. (B) All DNA radioactivity could be due to protein contaminations, because the specific activity of chromatin protein was determined to be more than 3,000 times higher than of DNA. The high affinity of the hormone to protein was also demonstrated by in vitro incubations, where it could be shown that the specific activity of DNA and protein was essentially proportional to the concentration of radiolabelled hormone in the organ homogenate, regardless of whether the animal was treated or whether the hormone was added in vitro to the homogenate.Carcinogens acting by covalent DNA binding can be classified according to potency on the basis of the Covalent Binding Index. Values of 10³–10⁴ have been found for potent, 10² for moderate, and 1–10 for weak carcinogens. Since estrone is moderately carcinogenic for the kidney of the male hamster, a CBI of about 100 would be expected. The actually measured limit of detection of 0.01 places covalent DNA binding among the highly unlikely mechanisms of action. Similar considerations can be made for the liver where any true covalent DNA binding must be below a level of 0.01. It is concluded that an observable tumor induction by estrone or estradiol is unlikely to be due to DNA binding.Paper presented at the Satellite Symposium of the European Society of Toxicology, Rome, March 29, 1983     

Mechanisms of antiplatelet and antithrombotic activity of midazolam in in vitro and in vivo studies

Dopamine regulates various physiological functions in the central nervous system and the periphery. Dysfunction of the dopamine system is implicated in a wide variety of disorders and behaviors including schizophrenia, addiction, and attention-deficit hyperactivity disorder. Medications that modulate dopamine signaling have therapeutic efficacy on the treatment of these disorders. However, the causes of these disorders and the role of dopamine are still unclear. Studying the dopamine system in a model organism, such as Caenorhabditis elegans, allows the genetic analysis in a simple and well-described nervous system, which may provide new insight into the molecular mechanisms of dopamine signaling. In this review, we summarize recent findings on pharmacological and biochemical properties of the C. elegans dopamine receptors and their physiological role in the control of behavior.     

Penetration and action of edoxudine in vitro and in vivo

The penetration of 5-ethyl-2'-deoxyuridine (edoxudine, Aedurid) from gel base with and without the addition of urea and other adjuvant has been studied in an in vitro model using guinea pig skin. The formulation of 3% edoxudine gel with 5% urea showed the best results. In vivo experiments on hairless mice infected intracutaneously with herpes simplex virus type 1 also showed this formulation's good efficacy as compared to other formulations.     

Extraction and determination of prednisolone in drugs and excipients in ointments and creams and the uniformity of distribution in prednisolone ointment

For the purpose of measuring the contents of prednisolone in low concentrated ointments and creams an instruction was elaborated that includes several steps of extraction, in the resulting solution of which the assay of the steroid by Blue Tetrazolium reaction will be done. The procedure permits the determination of prednisolone in presence of most of usual ingredients of ointment bases except wool alcohols. Also no influence is given by some remedies combined with prednisolone for topical application except coal tar solution. The results confirm a correct reflection of the steroid contents declared respectively the recovery of the steroid added to various ointment bases. Introducing discussion to content uniformity concerning low concentrated ointments is made, and some deviations are shown.     

Pharmacokinetics and tolerability of artesunate and amodiaquine alone and in combination in healthy volunteers

Objectives  The WHO recommends artemisinin-based combination therapies for treatment of uncomplicated falciparum malaria. At least 15 African countries have adopted artesunate plus amodiaquine as treatment policy. As no pharmacokinetic data on this combination have been published to date, we investigated its pharmacokinetic interactions and tolerability in healthy volunteers in Africa. Methods  In a randomized, three-phase, cross-over study, amodiaquine (10 mg/kg) and artesunate (4 mg/kg) were given as single oral doses to 15 healthy volunteers. Artesunate was given to all volunteers on day 0. On day 7 they received either amodiaquine or amodiaquine plus artesunate and the alternative regimen on day 28. The pharmacokinetics of artesunate and amodiaquine and their main active metabolites dihydroartemisinin and desethylamodiaquine were compared following monotherapy and combination therapy using analysis of variance. Results  Thirteen volunteers completed the study, and pharmacokinetic parameters could be determined for twelve volunteers. When given in combination, the mean AUC was lower for dihydroartemisinin [ratio 67% (95% CI 51–88%); P = 0.008] and desethylamodiaquine [ratio 65% (95% CI 46–90%); P = 0.015] when compared with monotherapy. Adverse events of concern occurred in four volunteers (27%): grade 3 transaminitis (n = 1), neutropaenia (n = 2), and hypersensitivity (n = 1). Conclusion  The total drug exposure to both drugs was reduced significantly when they were given in combination. The clinical significance of these interactions is unclear and must be studied in malaria patients. The frequency and nature of adverse events among the healthy volunteers were of concern, and suggest laboratory monitoring would be needed in malaria patients treated with artesunate plus amodiaquine.     

多廿烷醇与普伐他汀治疗高脂血症的疗效和安全性

目的评价多廿烷醇治疗高脂血症,特别是高胆固醇血症的疗效和安全性。方法多甘烷醇组(试验组,多廿烷醇10mg·d~(-1))和普伐他汀组(对照组,普伐他汀10 mg·d~(-1))各119例。进行随机、双盲、双模拟、阳性药物平行对照试验。观察2组降脂疗效和不良反应发生情况。结果经过12 wk治疗,多廿烷醇组总胆固醇(TC)、低密度脂蛋白胆固醇(LDL)、TC-高密度脂蛋白胆固醇(HDL-C)/ HDL-C、载脂蛋白B_(100)(Apo B_(100))、脂蛋白(Lpa)治疗前分别为(6.6±s0.7)、(4.0±0.6)、(0.10±0.03)、(3.3±0.5)mmol·L~(-1)、(260±184)mg·L~(-1),治疗后分别为(6.0±1.3)、(3.5±0.8)、(O.09±0.04)、(2.7±0.8)mmol·L~(-1)、(130±130)mg·L~(-1),治疗后各指标较治疗前均有非常显著差异(P<0.01)。普伐他汀组TC、LDL-C、TC-HDL-C/HDL-C、Apo B_(100)、Lpa治疗前分别为(6.7±0.8)、(4.1±0.7)、(0.10±0.03)、(3.4±0.5)mmol·L~(-1)、(279±240)mg·L~(-1),治疗后分别为(6.0±1.3)、(3.5±0.9)、(0.09±0.03)、(2.8±0.8)mmol·L~(-1)、(182±213)mg·L~(-1),治疗后各指标较治疗前均有非常显著差异(P<0.01)。但2组相比较,调脂作用相似,无显著差异(P>0.05)。不良反应方面,多廿烷醇组(9.2%)明显少于普伐他汀组(18.5%),2组有显著差异(P<0.05)。不良反应大多较轻微,不需停药能自行缓解。结论多廿烷醇10 mg·d~(-1)降脂效果与普伐他汀10 mg·d~(-1)的疗效相当,均能明显降低TC、LDL-C、TC-HDL-C/ HDL-C、Apo B_(100)、Lpa。多廿烷醇的安全性优于普伐他汀,不良反应轻微,耐受性好。     

Simultaneous Determination of Sulfation and Glucuronidation of Flavones in FVB Mouse Intestine in Vitro and in Vivo

Glucuronidation and sulfation are the two major phase II metabolic pathways for flavones, natural compounds that hold great potential for improving human health. We investigated the positional preference for sulfation and glucuronidation of seven structurally similar flavones in vitro and in situ. An FVB mouse intestinal perfusion model was used in addition to three small intestine S9 fractions catalyzing sulfation only (Sult enzymes), glucuronidation only (Ugt enzymes) or both (Sult and Ugt enzymes). In both the single and co‐reaction S9 systems, flavones containing 7‐OH groups were conjugated only at 7‐OH despite the presence of other hydroxyl groups, and 7‐OH glucuronidation was faster than sulfation (P < 0.05). The sulfation rate was enhanced in the Sult‐Ugt co‐reaction system, while glucuronidation was usually unchanged by the presence of Sult. In the intestinal perfusate, sulfation patterns were the same in the small intestine and colon, and the excretion rate of 7‐O‐sulfate was the fastest or second fastest. The excretion of 7‐O‐glucuronidates was faster in small intestine (P < 0.05) than in colon. The S9‐mediated sulfation rates of the different flavones were significantly correlated with the excretion rates of the same flavones from perfused intestine. In conclusion, flavone glucuronidation and sulfation rates were sensitive to minor changes in molecular structure. In intestinal S9 fractions, both Ugts and Sults preferentially catalyzed reactions at 7‐OH. The sulfation rate was significantly enhanced by simultaneous glucuronidation, but glucuronidation was unaltered by sulfation. Sulfation rates in mouse S9 fractions correlated with sulfation rates in perfused intestine. Copyright © 2011 John Wiley & Sons, Ltd.     

Stability and kinetics of hydrolysis of metronidazole monosuccinate in aqueous solution and in plasma

The kinetics of hydrolysis of metronidazole monosuccinate in aqueous solution at pH 1.5–10 and 60°C has been investigated. The decomposition was monitored by a high-performance liquid chromatographic method capable of determining the monosuccinate ester and the parent metronidazole simultaneously. At any given pH the reactions displayed strict first-order kinetics and were subject to specific acid-base catalysis; no general acid-base catalytic effect by various buffer substances was observed. Maximal stability was observed at pH 3–6, where the degradation rate was independent of pH indicating that intramolecular catalysis by the terminal carboxylate ion on the ester group is not involved in the hydrolysis reactions in this pH range. The lack of intramolecular catalysis is suggested to be due to the poor leaving ability of the strongly basic metronidazole alkoxide ion.The rates of conversion of the ester to metronidazole at 37°C in 80% human plasma and in 0.05 M phosphate buffer pH 7.40, respectively, were found to be nearly identical, $\text{t}{}_{\mathrm{<mtext>1</mtext><mtext>2</mtext>}}$~ 580 h, revealing that the degradation in plasma proceeds in the absence of enzymatic catalysis.     

Strain-dependency in motor activity and in concentration and turnover of catecholamines in synchronized rats

Circadian rhythm in motor activity was studied with an Animex motimeter in six strains of rats (ACI, BH, BS, DA, LEW, TNO) synchronized by a 12 hr light: 12 hr dark cycle. ANOVA revealed significant interstrain differences in motor activity as well as in the concentration and turnover of central noradrenaline and dopamine. Strain-dependent differences were also found with regard to tyrosine hydroxylase inhibition on motor activity. However, no significant interstrain correlations were found between endogenous concentration and/or turnover rates of the catecholamines and motor activity in normal and drug-treated rats.     

Comparative in vivo and in vitro studies of phenytoin protein binding and in vitro lipolysis in plasma of pregnant and nonpregnant rats

This investigation was designed to determine the cause of the changes in drug protein binding that occur in rat plasma, particularly in plasma from pregnant animals, during in vitro drug-protein binding measurements. In vivo estimates of phenytoin binding in plasma were obtained from steady-state CSF-plasma concentration ratios in pregnant and nonpregnant rats. Immediate ultrafiltration of heparin- or EDTA-anticoagulated plasma yielded phenytoin free fraction values that were in good agreement with in vivo estimates for nonpregnant rats but that were about one-third higher than in vivo estimates for pregnant animals. In vitro free fraction values tended to increase during incubation of plasma and/or during equilibrium dialysis. The concentrations of the four major endogenous free fatty acids were similar in plasma of pregnant and nonpregnant rats if determined immediately after blood collection. Six hours of incubation at 37 degrees C caused fatty acid concentrations to increase about fivefold and twofold in heparin-anticoagulated plasma from pregnant and nonpregnant animals, respectively. The corresponding increases in EDTA-anticoagulated plasma were only about twofold and 1.14-fold, respectively. These changes were associated with decreased plasma protein binding of phenytoin. The in vivo differences between pregnant and nonpregnant rats with respect to phenytoin binding in plasma are not due to differences in fatty acid concentrations, but the in vitro differences are due primarily to corresponding differences in free fatty acid concentrations if extensive in vitro lipolysis occurs.