Prevention of oral mucositis due to 5-fluorouracil treatment with oral cryotherapy

INTRODUCTION: One of the most common and important side effects of 5-fluorouracil (5-FU) is mucositis with ulcerations in the oral cavity. We investigated the effects of local cryotherapy on mucositis incidence administrated durng 5-FU treatment. METHODS: In a total of 99 courses, 5-FU and folinic acid combination chemotherapy was given to 40 patients. In our study, we considered every course as a single case, and cryotherapy was given to the same patient in one course but not given in the next. RESULTS: While mucositis developed in 6.7% of the courses given with cryotherapy, this ratio was 38.9% in courses given without cryotherapy. In the logistic regression analysis, development of mucositis had been found to correlate only with cryotherapy. Odds ratio (OR) = 11.5; in the 95% confidence interval (CI) = 3.2 - 41.9; (p = 0.001). DISCUSSION: Results of initial studies evaluating the effects of cryotherapy in preventing mucositis due to 5-FU based chemotherapy regimens were promising. We concluded that oral cooling prevents 5-FU induced mucositis. This effective prophylactic treatment should be used in patients who are at increased risk for developing 5-FU induced mucositis.     

氟尿嘧啶引起大鼠气管损伤及修复过程的观察及解析

目的 进行气管干细胞的定位研究。方法 使用氟尿嘧啶(5-FU)造成大鼠离体气管环的严重损伤,采用光镜、电镜及免疫组织化学链霉素抗生物素蛋白-过氧化物酶(SP)法检测增殖细胞核抗原(PCNA)动态观察气管黏膜的修复过程。结果 5-FU作用12h后,气管上皮脱落,可见少量间隔分布的类似裸核的细胞呈钉状位于基底膜上。去除5-FU 6h后,由扁平上皮覆盖;电镜下可见这些细胞缺乏分化;可见多个PCNA核染色阳性的细胞与1个阴性细胞(G0期细胞)的比例间隔分布;9h后,电镜下可见向纤毛细胞及黏液细胞分化;48h后,气管环全部由假复层纤毛柱状上皮细胞覆盖。结论 5-FU特异性地使进入细胞周期中的细胞变性坏死,而对G0期的细胞没有作用,残留于基底膜上的裸核样的G0期细胞增殖分化,再生出小黏液颗粒细胞和纤毛细胞进而修复损伤的气管环,证明气管干细胞位于气管上皮基底膜上的G0期细胞中。     

Mechanical loading of tissue engineered skeletal muscle prevents dexamethasone induced myotube atrophy

Journal of Muscle Research and Cell Motility - Skeletal muscle atrophy as a consequence of acute and chronic illness, immobilisation, muscular dystrophies and aging, leads to severe muscle...     

5-氟尿嘧啶诱导人肺腺癌A549细胞自噬

目的 探讨5-氟尿嘧啶(5-FU)是否诱导人肺腺癌A549细胞发生自噬.方法 吖啶橙(AO)荧光染色和透射电镜观察自噬泡的变化;细胞免疫化学法测定LC3-Ⅱ的表达;流式细胞术及吖啶橙染色结合激光扫描共焦显微镜检测细胞凋亡;DNA电泳检测凋亡梯形条带的产生.结果 吖啶橙荧光染色和透射电镜观察结果显示,5-氟尿嘧啶处理细胞...     

Aminoguanidine prevents ototoxicity induced by cisplatin in rats

Cisplatin (CDDP) is one of the most potent antineoplastic drugs, but its therapeutic use is limited by side effects such as ototoxicity. This study tested the effect of aminoguanidine (AG), a specific inhibitor of inducible nitric oxide synthase, on CDDP ototoxicity. Female Wistar albino rats were randomly assigned to 4 groups: saline controls (n = 7), CDDP (n = 7), CDDP plus AG (n = 7), and AG (n = 7). Rats in the CDDP group received a single injection of cisplatin (16 mg/kg, ip). Rats in the CDDP plus AG group received aminoguanidine (20 mg/kg, ip) twice daily on the day before and on 5 consecutive days after a single injection of CDDP (16 mg/kg, ip). Rats in the AG group received aminoguanidine (20 mg/ kg, ip) twice daily for 6 days. Distortion product otoacoustic emissions (DPOAEs) were elicited from the control and experimental animals utilizing a standard commercial otoacoustic emissions apparatus. DPOAEs were measured in the rats on day 0, prior to any drug administration, and on day 5. The initial baseline distortion product diagrams (DPgram) and input/output (I/O) function measurements gave similar results in all 4 groups. On day 5, there was significant deterioration of the DPgrams and I/O functions in the CDDP group; no significant changes of DPgrams and I/O functions were observed on day 5 in the other 3 groups. The median amplitudes of DPgrams and I/O functions revealed significant differences between the CDDP group and the other 3 groups. These results suggest that AG had a preventive effect against CDDP ototoxicity. In summary, this study indicates that AG prevents the cochlear dysfunction and hearing loss induced in rats by a single dose of CDDP.     

Neurogenic stomach neoplasms induced by nitrosomethylures in Syrian hamsters]

In the experiment with inoculation of N-nitroso-N-methylurea (a maximum total dose of 7.5 mg) to Syrian hamsters, tumors developed in 20 out of 25 animals surviving the time of the occurrence of the first tumor (31 weeks). Out of 35 tumors 17 developed at the site of inoculation: in the left cheek pouch (of them 12 embryonal rhabdomyoblastomas), 11 in the stomach (of them 6 neurogenic), and 7 in other organs (skin, liver, adrenals, hemopoietic system). The paper describes the histological pattern of 6 neurogenic tumors of the stomach in which all the elements of the nervous system have been found: ganglionic cells, neuroglia, and nerve stems. On the basis of some signs the authors classify these tumors as malignant.     

Insulin therapy prevents spontaneous recovery from streptozotocin-induced diabetes in Syrian hamsters

Summary Streptozotocin (Sz) given as a single dose of 50 mg/kg body wt. caused severe diabetes in Syrian hamsters. However, the level of blood glucose decreased gradually after 21 days post-Sz and reached the near normal level at 70 days in 90% of hamsters. The recovery from diabetes was associated with the regeneration of the-cells of islets and a reduction in the initially increased number of- and-cells. Daily treatment of diabetic hamsters with insulin was associated with the persistence of severe diabetes, lack of or minimal tendency for-cell regeneration and sustained hyperplasia of- and-cells in 90% of hamsters. Insulin also inhibited DNA synthesis (as measured by incorporation of tritiated thymidine), in ductal, ductular and acinar cells in Sz-pretreated hamsters but not in normoglycemic control hamsters treated with insulin alone. The results demonstrate a deleterious effect of exogenous insulin in the course of Sz-induced diabetes in hamsters.This work supported by grant CA38922, Laboratory Core grant CA36727, NCI/NIH, and SIG-16, American Cancer Society     

Immunity to tumors induced by herpes simplex virus in hamsters]

Preparations of early herpes simplex virus antigen (VIA) and specific antibodies to it were used to induce active and passive immunity to herpes virus-induced tumors in experimental animals. The results demonstrated the increased resistance of animals to transplantation of tumor cells due to vaccination with VIA-containing preparations. Thus, in VIA-vaccinated animals there was a delay in the development of tumors and the survival time was significantly higher than in the controls. The sera of these animals contained antibodies to VIA in high titres. Experiments with passive immunization also gave encouraging results.     

Maternal experience prevents pup-killing in mice induced by peripheral anosmia

The ability of experience to modify pup-killing by a peripheral anosmia was investigated in a 2 × 2 design in which experience and anosmia were manipulated. Anosmia induced by zinc sulfate flush of the nasal epithelium resulted in pup-killing in 13 of 15 primiparous litters, whereas only 2 of 15 multiparous mothers were pup-killers. These results suggest that primiparous mothers depend heavily on olfaction and that a dichotomy exists between the peripheral chemical induced anosmia (modifiable by experience) and the central, whole bulb aspiration induced anosmia, not modifiable by experience.     

Sulindac prevents esophageal adenocarcinomas induced by gastroduodenal reflux in rats

PURPOSE: It is known that cyclooxygenase (COX)-2 expression is increased in Barrett's esophagus and esophageal adenocarcinomas. We studied COX-2 expression and the effect sulindac has on the genesis of Barrett's esophagus and adenocarcinoma in rats undergoing esophagogastroduodenal anastomosis (EGDA). MATERIALS AND METHODS: Fifty-one rats were divided into a control group (n=27), a 500 ppm sulindac-treated group (n=15) and 1000 ppm sulindac-treated group (n=9). Randomly selected rats were killed by diethyl ether inhalation at 20 and 40 weeks after surgery. RESULTS: At 40 weeks, rats treated with 1000 ppm sulindac showed narrower esophageal diameter and milder inflammation than the control rats. At 40 weeks, the incidence of Barrett's esophagus was similar between control and sulindac-treated groups, but the incidence of adenocarcinoma was significantly lower in the 1000 ppm sulindac-treated group than either the control or 500 ppm sulindac-treated groups. COX-2 was significantly increased in the lower esophagus of control rats killed at 40 weeks. Cyclin D1 expression was negligible in the sulindac- treated group compared with the control group. CONCLUSION: We suggest that the chemopreventive effect of sulindac is related to decreased COX-2 and cyclin D1 expression, which may be influenced by reduced inflammation.     

Passive immunization prevents induction of Lyme arthritis in LSH hamsters.

We determined that sera obtained from hamsters infected with Borrelia burgdorferi could prevent the induction of Lyme arthritis. When irradiated hamsters were administered immune serum and subsequently challenged with B. burgdorferi, no evidence of infection was detected. Recipients failed to develop swelling of the hind paws, and no histopathologic changes were detected. In addition, B. burgdorferi was not recovered from tissues of hamsters that were passively immunized. By contrast, irradiated hamsters that were administered normal hamster serum or saline and infected with the Lyme spirochete developed arthritis. Extensive histopathologic changes occurred in the hind paws and knee joints, and spirochetes were recovered from most of the tissues examined. These results show that immune serum can confer complete protection on recipient hamsters to challenge with B. burgdorferi.     

DES induced sperm destruction in Lakeview hamsters

DES toxicity on sperm production after five consecutive sublethal i.p. injections of 8, 40 and 200 mg/kg was investigated in Lakeview hamsters. Testis weight, caudal sperm number, sperm morphology and body weight were monitored at week 1, 4 and 10 after treatment. DES doses of 8 mg/kg or above caused complete destruction of caudal sperm and reduced testes size to almost 10% of control within 10 weeks. Some sperm production resumed after the 8 mg/kg dose at the 10th week but more than half of these cells were abnormal in shape. Body weights remained almost stable for the first 4 weeks and then increased gradually by 25% at the 10th week.     

链球菌蛋白对5-氟尿嘧啶引起的小鼠脾细胞增殖抑制及凋亡的拮抗作用

目的 研究32080株链球菌蛋白体外对5-氟尿嘧啶(5-Fu)引起的小鼠脾细胞增殖抑制及凋亡的影响并探索其相关机制.方法 MTT法检测链球菌蛋白和5-Fu对小鼠脾细胞增殖活性的影响;流式细胞仪分析链球菌蛋白和5-Fu对脾细胞周期分布、凋亡率及线粒体膜电位等的影响.结果 不同浓度的链球菌蛋白(10～100μg/mL)能显著促进脾细胞增殖,并可拮抗5-FU所致的脾细胞增殖抑制作用;链球菌蛋白(50μg/mL)能明显促进5-FU阻滞的脾细胞通过S期,进入G2/M期,恢复细胞的有丝分裂进程;链球菌蛋白(50μg/mL)明显拮抗5-FU引起的脾细胞线粒体膜电位下降(P＜0.01),降低5-FU引起的脾细胞凋亡率(P＜0.01).结论 链球菌蛋白对小鼠脾细胞具有明显的增殖活化作用,拮抗5-FU对细胞的增殖抑制作用,促进5-FU抑制的脾细胞进入细胞分裂周期,稳定其线粒体膜电位,抑制细胞线粒体途径凋亡.     

Autophagy induced by resveratrol prevents human prion protein-mediated neurotoxicity

Our previous study revealed that resveratrol blocks prion protein peptide PrP(106-126)-induced neurotoxicity. However, the mechanism of resveratrol-mediated neuroprotection in prion diseases is not clear. Resverstrol initiates neuroprotective effects via the activation of autophagy, which protects organelles, cells, and organisms against misfolded protein-disorders, including Alzheimer's disease and Parkinson's disease via regulation of mitochondrial homeostasis. Thus, we focused on elucidating the mechanisms responsible for resveratrol-mediated neuroprotection related to mitochondrial homeostasis as a result of autophagy activation. Resveratrol prevented PrP(106-126)-induced neuronal cell death by activating autophagy. Moreover, resveratrol-induced autophagy prevented the PrP(106-126)-induced reduction in mitochondrial potential and translocation of Bax to the mitochondria and cytochrome c release. Our results indicate that treatment with resveratrol appears to protect against neurotoxicity caused by prion protein peptides and the neuroprotection is induced by resveratrol-mediated autophagy signals.