Caffeic Acid Phenethyl Ester Ameliorated Ototoxicity Induced by Cisplatin in Rats

Abstract

Caffeic acid phenethyl ester (CAPE), an active component of propolis, exhibits antioxidant properties. This experimental study was designed to determine the effect of CAPE on ototoxicity induced with cisplatin. Twenty-four adult Wistar albino rats were divided into four groups: cisplatin (n=6), saline (n=6), CAPE (n=6), and cisplatin plus CAPE (n=6). Rats were tested before and 5 days after cisplatin treatment with or without chemo protection. The Distortion Product Otoacoustic Emissions (DPOAEs) were elicited from the control and experimental animals utilizing the standard commercial Otoacoustic Emission (OAEs) apparatus. The animals in all groups were sacrificed under general anesthesia on the fifth day following last OAE measurements. For biochemical investigations, the blood samples were drawn from inferior vena cava

On day 0, the initial baseline DPOAEs measurement results presented similar values while comparing the groups in drug free phase (p>0.05). On day 5, intrasubject measurement parameters of DPgrams and I/O functions of cisplatin group were significantly deteriorated (p<0.05). The second measurements of the other groups revealed no significant differences between their DPgrams and I/O functions in all frequencies (p>0.05). Among the biochemical parameters, plasma xanthine oxidase (XO) activity was found to be more elevated in the cisplatin group than the saline group (p<0.05). CAPE led to more decreased XO activity than cisplatin (p<0.05). The results of this study show that prophylactic administration of CAPE for cisplatin ototoxicity ameliorated hearing deterioration in rats.     

Efficacy of Teicoplanin,Administered in Two Different Regimens,in the Treatment of Experimental Endocarditis Due to Enterococcus faecalis

Abstract

Using a rabbit model of endocarditis, we studied the efficacy of teicoplanin against a strain of Enterococcus faecalis resistant to ampicillin. Rabbits were randomly assigned to receive no antibiotics, teicoplanin 12 or 18 mg/kg of body weight every 12h, for 9 days. The effect of treatment on bacterial counts of vegetations and survival of the animals was evaluated at the end of treatment and 10 days thereafter. The two treatment regimens of teicoplanin produced peak serum levels 18.51±1.84 and 34.66±4.19 μg/ml, and trough levels above 10×MIC of teicoplanin for the infecting organism. Both regimens resulted in significant bacterial reduction in the vegetations as compared to the control group (p<0.001). The drug prevented relapse of the infection 10 days after discontinuation of treatment. By increasing the teicoplanin dosage no additional therapeutic benefit was observed in terms of bacterial killing, sterilization of the vegetations, and survival of the animals, although the higher doses gave numerically superior results. These findings may have meaning for the optimum use of teicoplanin in the treatment of enterococcal endocarditis.     

In Vitro Release of Fusidic Acid and Teicoplanin from Cancellous Bone Allografts

Abstract

The characteristics of cancellous bone allografts as carriers of fusidic acid and teicoplanin are described. Particles of cancellous bone were compressed into a wire-mesh cylinder; five replicas were impregnated for one hour into fusidic acid; and another five for one hour into teicoplanin. Elution was estimated daily. Concentrations of fusidic acid and teicoplanin were determined by a microbiological assay. Both antibiotics were eluted at very high concentrations within the first days. Allografts impregnated in fusidic acid provided concentrations above 20 μg/ml for 20 days. Eluted teicoplanin after day 4 was below 10 μg/ml. It is concluded that cancellous bone allografts may allow adequate In Vitro elution of fusidic acid but not of teicoplanin. The latter results support their application in experimental models of osteomyelitis.     

Anticancer Effects of Thymoquinone,Caffeic Acid Phenethyl Ester and Resveratrol on A549 Non-small Cell Lung Cancer Cells Exposed to Benzo(a)pyrene

Background: Phytochemical compounds are emerging as a new generation of anticancer agents with limitedtoxicity in cancer patients. The purpose of this study was to investigate the potential effcts of thymoquinone,caffeic acid phenylester (CAPE) and resveratrol on inflammatory markers, oxidative stress parameters, mRNAexpression levels of proteins and survival of lung cancer cells in Vitro. Materials and Methods: The A549 cellline was treated with benzo(a)pyrene, benzo(a)pyrene plus caffeic acid phenylester (CAPE), benzo(a)pyreneplus resveratrol (RES), and benzo(a)pyrene plus thymoquinone (TQ). Inflammatory markers, oxidative stressparameters, mRNA expression levels of apoptotic and anti-apoptotic proteins and cell viability were assessedand results were compared among study groups. Results: TQ treatment up-regulated Bax and down-regulatedBcl2 proteins and increased the Bax/Bcl2 ratio. CAPE and TQ also up-regulated Bax expression. RES and TQdown-regulated the expression of Bcl-2. All three agents decreased the expression of cyclin D and increased theexpression of p21. However, the most significant up-regulation of p21 expression was observed in TQ treatedcells. CAPE, RES and TQ up-regulated TRAIL receptor 1 and 2 expression. RES and TQ down-regulated theexpression of NF-kappa B and IKK1. Viability of CAPE, RES and TQ treated cells was found to be significantlydecreased when compared with the control group (p=0.004). Conclusions: Our results revealed up-regulationof the key upstream signaling factors, which ultimately cause increase in their regulatory p53 levels affectingthe induction of G2/M cell cycle arrest and apoptosis. Overall these results provide mechanistic insights forunderstanding the molecular basis and utility of the anti-tumor activity of TQ, RES and CAPE.     

Economic Evaluation of Linezolid Versus Teicoplanin for the Treatment of Infections Caused by Gram-Positive Microorganisms in Spain

Abstract

The aim of this study was to perform a comparative cost-effectiveness analysis of linezolid vs teicoplanin (i.v., switching to oral/i.m. respectively) in Spain. A decision tree model was used with the results of a randomized, comparative, controlled clinical trial with linezolid vs teicoplanin in the treatment of infections caused by Gram-positive microorganisms, with a timeline of 31 days. The efficacy endpoint was the percentage of patients with clinical healing or improvement in their infection. Direct medical costs were included using Spanish 2005 prices. Average cost per patient, average cost-effectiveness ratio and several sensitivity analyses were carried out. In the intent-to-treat (ITT) analysis linezolid obtained a higher percentage of therapeutic success than teicoplanin (95.5% vs 87.6% respectively, p = 0.005), both with similar tolerability. The average cost per treated patient was €8,064.76 for linezolid vs €8,727.36 for teicoplanin, with an incremental cost of €622.59 (?7,6%). Linezolid yielded a lower average cost-effectiveness ratio, €8,444.78 (8,195.90 – 8,709.25) than teicoplanin, €9,962.74 (9,465.68 – 10,502.23), with a slight reduction in average cost per successfully treated patient of 15.2% (€1,517.96). The results were robust to the sensitivity analysis. In conclusion, linezolid is a more cost-effective option than teicoplanin in the treatment of infections caused by Gram-positive microorganisms, since it offers superior clinical benefits with a lower use of associated resources.     

全反式维甲酸治疗大鼠C6脑胶质瘤的实验研究

[目的]探讨全反式维甲酸治疗大鼠C6脑胶质瘤的疗效及其机制。[方法]建立大鼠C6脑胶质瘤模型,腹腔注射全反式维甲酸后,MRI检测胶质瘤的体积变化,免疫组化检测胶质纤维酸性蛋白（GFAP）的表达并观察生存期。[结果]治疗组较对照组肿瘤体积明显减小（P〈0.05）;生存期延长（P〈0.05）;GFAP表达增加（P〈0.05）。GFAP的表达同肿瘤体积呈负相关（P〈0.05）。[结论]全反式维甲酸治疗可延长荷瘤鼠生存期,其机制与上调GFAP的表达有关。     

二联与多西他赛三联疗法对低分化胃癌的治疗观察

目的 对比二联与多西他赛三联疗法对低分化胃癌的治疗效果与安全性.方法 择取80例低分化胃癌患者作为研究对象,根据患者对治疗的意愿分为2组,即二联组(30例)与三联组(50例).二联组采用二联方案(奥沙利铂+替吉奥胶囊)治疗,三联组采用三联方案(多西他赛+顺铂+氟尿嘧啶)治疗.观察2组近期临床疗效、治疗前后外周血T淋巴细胞水平及治疗期间药物的毒副作用.结果 三联组总有效率(32/50,64.00%)高于二联组(12/30,40.00%)(P<0.05).治疗后三联组CD4+水平高于二联组(P<0.05).三联组神经毒性(20/50,40.00%)、粒细胞减少(23/50,46.00%)、手足综合征(10/50,20.00%)的发生率高于二联组(5/30,16.67%)、(7/30,23.33%)、(2/30,6.67%)(P<0.05).结论 多西他赛+顺铂+氟尿嘧啶三联疗法对低分化胃癌的治疗效果优于奥沙利铂+替吉奥胶囊二联疗法,但三联疗法的不良反应发生率高于二联疗法,临床工作中应结合患者的病情进行灵活选择.     

Combined therapy of teicoplanin and caffeic acid phenethyl ester (CAPE) in the treatment of experimental mediastinitis in the rat

Post-sternotomy mediastinitis affects 1-3% of patients undergoing cardiac surgery and is lethal in 10-47% of these patients. We investigated the effect of an antioxidant/anti-inflammatory agent, caffeic acid phenethyl ester (CAPE), in the attenuation of inflammatory response induced by methicillin-resistant Staphylococcus aureus (MRSA) infection in a rat experimental mediastinitis model. Rats, divided into six equal groups, received MRSA precolonized stainless steel wire pieces implanted into their mediastinal spaces. Control group and CAPE control group received saline and CAPE 10 micromol/kg.day(-1 )respectively, where Group A received a single dose of teicoplanin 24 mg/kg i.m. for the first day and then 12 mg/kg.day(-1) . Group B received teicoplanin as in Group A plus CAPE 10 micromol/kg. day(-1 )intra-peritoneally. Group C received teicoplanin 60 mg/kg i.m. for the first day and then 30 mg/kg.day(-1 )and Group D received teicoplanin as in Group C plus CAPE 10 micromol/kg.day(-1) . By the end of 14 days rats were sacrificed and serum malondialdehyde (MDA), myeloperoxidase (MPO), nitric oxide (NO), urea and creatinine levels were evaluated. Mediastinal organ tissues were collected for histopathological analysis. Infection rates in all the drug-treated groups were lower than the control groups ( P=0.002) but statistical significance was attained only between the groups A and D ( P=0.018). In connective tissues and the peribronchial area polymorphonuclear leukocytic (PNL) infiltration in the treatment groups, although becoming very close, did not reach statistical significance (P =0.053, P=0.075, respectively). PNL infiltration especially in the peribronchial tissues of the Group B animals was found to be significantly less than the Control and CAPE Control groups with P values of 0.013 and 0.010, respectively. MDA and MPO levels were significantly lower in the treatment groups ( P<0.001 and P<0.001 respectively). Levels of the degradation products of NO were lower in treatment groups compared to two control groups (P=0.003, P= 0.005). NO levels in Group D were lowest among all treatment groups ( P=0.001). It has been demonstrated that although bacterial colonization can be controlled in mediastinitis, the inflammatory response persists. The combination of an antioxidant / anti-inflammatory agent, CAPE, added to standard antibiotic therapy might be effective in the treatment of post-sternotomy mediastinitis due to MRSA.     

升高血压联合化疗治疗脑胶质瘤的实验研究

目的:观察利用血管紧张素Ⅱ(AgⅡ)升高血压状态下,钙离子拮抗剂尼莫地平(NMD)和化疗药物联合使用对移植性鼠脑胶质瘤的治疗效果,为临床上脑胶质瘤的化疗提供更合理的方法和理论依据。方法:通过立体定向技术制备移植性鼠脑胶质瘤模型,利用氢清除法测定变压条件下肿瘤和正常脑组织血流量,比较NMD对照组,BCNU、Vm-26、DDP联合化疗组,联合化疗加升压组对肿瘤鼠存活期,肿瘤抑制率及肿瘤病理学影响。结果:AgⅡ诱导高血压状态下,肿瘤组织内血流量明显增加,而其它部位脑组织血流量无明显变化。联合化疗加升压组的存活时间为44.8±11.3天,与联合化疗组的存活时间26.8±5.9天相比,差异显著(P<0.01),而且联合化疗加升压组抑瘤率高于联合化疗组。结论:在AgⅡ诱导高血压状态,通过钙离子拮抗剂与化疗药物的联合应用,可以提高脑胶质瘤的化疗效果。     

Interstitial Docetaxel (Taxotere), Carmustine and Combined Interstitial Therapy: a Novel Treatment for Experimental Malignant Glioma

Docetaxel (Taxotere) is a hemisynthetic, anti-cancer compound with good preclinical and clinical activity in a variety of systemic neoplasms. We tested its activity against malignant gliomas using local delivery methods. Antitumor activity was assessed in vitro against human (U87 and U80 glioma) and rat brain-tumor (9L gliosarcoma and F98 glioma) cell lines. For in vivo evaluation, we incorporated docetaxel into a biodegradable polymer matrix, determined associated toxicity in the rat brain, and measured efficacy at extending survival in a rat model of malignant glioma. Also, we examined the combined local delivery of docetaxel with carmustine (BCNU) against the experimental intracranial glioma. Rats bearing intracranial 9L gliosarcomas were treated 5 days after tumor implantation with various polymers (placebo, 5% docetaxel, 3.8% BCNU, or 5% docetaxel and 3.8% BCNU combination). Animals receiving docetaxel polymers (n = 15, median survival 39.1 days) had significantly improved survival over control animals (n = 12, median survival 22.5 days, P = 0.01). Similarly, animals receiving BCNU polymers (n = 15, median survival 39.3 days, 13.3% long-term survivors) demonstrated an increase in survival compared to the controls (P = 0.04). Animals receiving the combination polymers demonstrated a modest increase in survival compared to either chemotherapeutic agent alone (n = 14, median survival 54.9 days, 28.6% long-term survivors) with markedly improved survival over controls (P = 0.003). We conclude that locally delivered docetaxel shows promise as a novel anti-glioma therapy and that the combination of drug regimens via biodegradable polymers may be a great therapeutic benefit to patients with malignant glioma.     

The role of the tissue adhesive fibrin seal (FS) in esophageal anastomoses

Following Surgical Removal Of Esophageal Tumors, Leakage And Medistinitis Is A Frequent And Often Fatal Complication. A New Method Has Been Developed To Seal Suture Lines In The Esophagus With Preparations Containing Fibrinogen, Cold Insoluble Globulin, Factor Xiii, Antiplasmin, Platelet Growth Factor, Thrombin, And Calcium Chloride. In Experimental Animals Operated On By Standard Methods, Esophageal Leakage Developed In 50% Of The Animals And Death In 40%. By Contrast, In Treated Animals, Esophageal Leak And Death Developed In Only 20%. More Adhesions Were Found In Treated Animals Than In Control Animals.     

An Open Study of Teicoplanin in the Treatment of Gram-Positive Infections

Summary

Teicoplanin, a new glycopeptide antibiotic similar to vancomycin, was evaluated in treating 36 hospitalized patients suffering from various Gram-positive infections. The 36 patients received teicoplanin once daily as a mean intravenous injection of 550 mg/day (range 200-800 mg/day). Previous antimicrobial therapy was used in 28% of patients. The mean duration of therapy was 7.5 days (range 3-38 days). The overall clinical success rate was 94%. 24/36 patients (66%) had positive microbiology. Elimination of the pathogens was seen in 75% of all evaluable cases. Four patients with early prosthetic valve endocarditis due to coagulase negative Staphylococcus (3 patients) and Proptontbacterium acnes (1 patient) had a favorable clinical and microbiological outcome. No adverse drug reactions were observed. Teicoplanin is safe and effective in the therapy of many different infections caused by Gram-positive bacteria.     

Combined Hyperthermia and Radiation Therapy for Treatment of Hepatocellular Carcinoma

Background: There is no doubt that hyperthermia is one of the powerful radiosensitizers. Finding a proper mechanismworking in hyperthermia/radiation combination is still pronounced challenge. Objectives: This study is focusing onthe anti-cancer activities (anti-proliferative, anti-angiogenic and antiapoptotic) of thermoradiotherapy. Materials andMethods: Liver cancer cell line (HepG2) was treated by 37oC, 40oC and 43oC hyperthermia degrees combined withthree radiation doses (2 Gy, 4 Gy and 8 Gy) for 24, 48 and 72 hrs. Cell viability, apoptotic/necrotic cell screening,apoptotic (BAX and FasL) and antiapoptotic (BCL-2 and GRP78) genes, and pro-angiogenic mediators [vascularendothelial- (VEGF) and Platelet derived-growth factors (PDGF) ware investigated. Results: Our data showed that 40oCtemperature combined with 4 Gy radiation gives a significant decrease (p<0.05) in cell viability. Maximum cytotoxicitywas reported 48 hr post-treatment followed by slight restoration of cell viability after 72 hr. Compared with untreatedcells, only 5% of viable cells with a high percentage of apoptotic (31%) and necrotic (63%) cells were demonstratedin 40oC/4 Gy/48 hr group. Expression of pro-apoptotic genes (BAX and FasL) were increased after hyperthermia withapparent elevation in 40oC/4 Gy/48 hr group coincides with moderate expression of antiapoptotic BCL-2 and GRP78genes. A significant reduction (p<0.001; p<0.05) in VEGF and PDGF levels; respectively was shown at 40oC/4 Gy/48hr group. Conclusions: This pilot study proposed 40oC mild temperature hyperthermia as a favorable hyperthermalcondition with 4 Gy radiotherapy in HCC treatment. A further research has to be performed considering an applicationof more than one session of radiothermal therapy at 40oC/4 Gy for total abrogation of cancer cells.     

乳腺癌化疗和内分泌治疗是否应当联合使用

在乳腺癌治疗中，化疗和内分泌治疗是否可以联合应用一直是大家关注及争论的热点。该文分别从术后辅助治疗和复发转移后解救治疗两个方面，回顾国际大规模临床试验的结果，结合当前乳腺癌治疗的指导原则和作者的经验，认为乳腺癌化疗和内分泌治疗应当合理地序贯应用，而不是同时联合应用。     

唑来膦酸联合放疗治疗骨转移瘤的临床观察

目的：探讨唑来膦酸联合放疗治疗骨转移瘤的临床疗效和安全性。方法选择60例骨转移瘤患者,随机均分为2组,观察组30例给予唑来膦酸联合放疗,对照组30例仅单纯行放疗。结果观察组镇痛有效率93.3％,高于对照组的73.3％（P＜0.05）;骨转移灶的影像学有效率66.7％,对照组56.7％,差异无统计学意义（ P＞0.05）。2组毒副反应相似,均在可控制范围内。结论唑来膦酸联合放疗治疗骨转移瘤疗效较满意,毒副反应可耐受。     

白细胞介素12及白细胞介素2对大鼠肝癌的联合基因治疗研究

目的：研究利用小鼠白细胞介素12(mIL12)和人白细胞介素2(hIL2)基因对大鼠肝癌进行联合基因治疗的可行性和疗效。方法：构建携带mIL12和hIL2基因的逆转录病毒载体，转染包装细胞后对实验性肝癌大鼠进行肝癌局部注射，观察对肝癌细胞的生长抑制作用及其对大鼠的免疫功能变化、毒性反应。结果：携带mIL12/hIL2基因的重组逆转录病毒在肿瘤内局部注射明显抑制了肝肿瘤的生长。肝癌接种后第1,3,5,7天治疗组大鼠35 d生存率分别为100%,100%,30%,10%。IL12+IL2治疗组平均生存时间明显高于生理盐水对照组（P＜0.01)、逆转录病毒空载体对照组（P＜0.01)、IL2治疗组（P＜0.01)和IL12治疗组（P＜0.05)。治疗后肝癌组织中浸润的淋巴细胞明显增多。结论：肝癌局部注射携带mIL12和hIL2基因的逆转录包装细胞株可明显抑制肝癌细胞的生长，早期治疗优于晚期治疗。     

恶性肿瘤综合治疗中高营养疗法的地位

本文报告了１１７例各类癌症患者的高营养治疗效果，其中６５例舌癌术后经鼻腔胃插管施行了流质高蛋白饮食治疗，保证了手术创口顺利愈合；其余５２倒包括胃癌、食管癌、结肠癌及晚期肺癌患者施行了完全静脉高营养疗法，患者负氮平衡于３～３４天内得到了纠正。术前患者在两周内纠正了贫血及低蛋白血症，为手术创造了良好条件，术后恢复顺利，为以后的化疗奠定了基础。讨论中指出了高营养治疗可明显地提高免疫功能，在并用化疗时可提高癌患者的治愈率。