Relationship between dose of methotrexate, apoptosis, p53/p21 expression and intestinal crypt proliferation in the rat

Abstract Previous studies have shown that apoptosis is induced by cytotoxic chemotherapy and precedes hypoproliferation of intestinal crypt cells. However, the relationship between the degree of intestinal apoptosis and crypt cell hypoproliferation may not be directly related. The purpose of this study was to investigate the relationship between apoptosis and hypoproliferation with increasing doses of chemotherapy. Eleven groups of breast cancer-bearing DA rats were treated with two doses of methotrexate (MTX) i. m. at varying concentrations (0.5, 1.5, 2.5 and 5.0 mg/kg) or saline (control). Animals were killed at 6 or 24 h following treatment. The small and large intestines were examined for apoptosis, villous area (small intestine), crypt length and mitotic count per crypt. Immunohistochemical expression of p53 and p21^waf1/cip1 (p21) were examined quantitatively. Data were analysed using Peritz F-test. Low dose MTX (0.5 mg/kg) did not change p53 expression at 6 h but induced a 15-fold increase in apoptosis in the crypts of the small intestine. This was associated with only a minor reduction in crypt cell proliferation. Higher doses of MTX increased p53 expression and caused a lower (7-fold) but more prolonged peak of apoptosis that was accompanied by reduced villous area, shortened crypts and a more profound reduction in crypt cell proliferation. Unlike the small intestine, apoptosis in the colon was 10-fold lower, proportional to the dose of MTX and did not induce overt damage. Expression of p21 did not change with any dose at either timepoint. We conclude that apoptosis is not always associated with crypt cell hypoproliferation and that the small intestine can recover after low dose MTX despite a heightened peak of apoptosis of crypt cells.     

Expression of IL-6, IL-10, IL-17 and IL-33 in the peri-implant crevicular fluid of patients with peri-implant mucositis and peri-implantitis

ObjectivesThe aim of this study was to compare the levels of IL-6, IL-10, IL-17 and IL-33 in the peri-implantar crevicular fluid (PICF) and in parotid gland saliva (PGS) of healthy patients, and peri-implantitis and peri-implant mucositis patients.Materials and methodsThe PICF was collected from 40 implants as follows: 10 peri-implant mucositis patients, 20 peri-implantitis patients and 10 healthy patients. The PICF and PGS samples collected from each patient were quantified for IL-6, IL-10, IL-17 and IL-33 by enzymatic immunosorbent assay (ELISA).ResultsIL-6, IL-17 and IL-33 levels on PIFC were significantly higher in peri-implantitis group when compared to healthy group. IL-17 and IL-33 levels in PIFC were significantly higher in peri-implant mucositis group than in healthy group. There was no significant difference when comparing IL-6, IL-10, IL-17 and IL-33 levels in PGS among healthy, peri-implant mucositis and peri-implantitis groups.ConclusionsTherefore, as in patients with peri-implantitis there were significantly higher levels of IL-6, IL-17 and IL-33 in PICF, we believe that these cytokines were intensifying local inflammatory process, and contributing to clinical aspects such as increased marginal bleeding and probing depth found in patients with peri-implantitis. Furthermore, as IL-17 and IL-33 were increased in patients with peri-implant mucositis, hypothesized that these cytokines were also contributing to the inflammatory process observed in this disease.     

More than skin deep

We present the case of a woman in her 50s with past medical history significant for psoriasis treated with methotrexate on a stable dose for the past 20?years, diabetes mellitus and chronic kidney disease. In the setting of a long flight, dehydration and non steroidal anti-inflammatory drug consumption, the patient presented to the emergency department with oral mucositis and cutaneous erosions and ulcers of the psoriasis plaques. MTX levels were normal corroborated by three different measurements in 24?h. Initially the complete blood count tests were significant for macrocytic, thrombocytopenia (82.000 10³/L) and impaired kidney function. The patient was diagnosed of acute methotrexate toxicity and started on intravenous folinic acid. In 24?h the patient developed severe pancytopenia. She required treatment with colony-stimulating factors, platelet and blood transfusions. After 10?days, the CBC improved to normal levels and the cutaneous lesions resolved.     

康复新液对头颈部肿瘤放疗后重度放射性口腔黏膜炎的治疗作用及对唾液腺的保护作用

目的探讨康复新液对头颈部肿瘤放疗后重度放射性口腔黏膜炎的治疗作用及对唾液腺的保护作用。方法选取2016年10月—2019年10月在鄂东医疗集团市中心医院完成根治性放疗且发生重度放射性口腔黏膜炎的116例头颈部肿瘤患者,按随机数字表法将所有患者分为治疗组和对照组,每组各58例。在常规治疗的基础上,治疗组给予康复新液含服,10 ml/次,3次/d;对照组给予复方氯己定含漱液10~20 ml含漱,2次/d。分别于治疗前、治疗后第7天、治疗后第14天测量两组患者唾液流率、口腔p H值,应用ELISA法检测唾液淀粉酶及表皮生长因子水平。比较两组患者治疗疗效、口腔黏膜愈合时间及口腔真菌感染发生率。结果治疗后两组患者的唾液流率及口腔p H值均呈升高趋势(P<0.01);且治疗后治疗组患者唾液流率及口腔p H值均显著高于对照组患者同期,两组比较差异均有统计学意义(P<0.01)。治疗后两组患者AMS和EGF水平均呈升高趋势(P<0.01);且治疗后治疗组患者AMS和EGF水平显著高于对照组患者同期水平(P<0.01)。治疗后治疗组口腔黏膜愈合时间优于对照组,两组比较差异有统计学意义(t=6.167,P<0.01)。治疗第7天,治疗组有7例发生口腔真菌感染,对照组有16例发生口腔真菌感染,治疗组口腔真菌感染发生率为12.07%,对照为27.59%,两组比较差异有统计学意义(χ²=4.393,P<0.05)。治疗后治疗组总有效率为89.66%(52/58),对照组总有效率为68.97%(40/58),两组比较差异有统计学意义(χ²=7.565,P=0.006)。结论康复新液能提高对重度放射性口腔黏膜炎的治疗疗效,促进损伤黏膜的愈合,降低口腔真菌感染的发生率,其机制可能与促进唾液淀粉酶及表皮生长因子的分泌,提高唾液流率及口腔p H值有关。     

表皮生长因子受体在老年大肠癌中的表达及临床意义

目的探讨表皮生长因子受体（EGFR）在老年大肠癌组织中的表达及其临床意义.方法采用免疫组化SABC法对87例大肠癌、14例大肠炎性黏膜和26例大肠腺癌样息肉进行检测。结果 EGFR在大肠炎性黏膜、腺瘤样息肉和大肠癌中阳性率分别为21.43%、46.15%和54.02%，其中RGFR在炎性黏膜中表达率明显低于腺瘤样息肉和大肠癌（P〈0.05）；EGFR表达与大肠癌浸润深度和淋巴结转移有相关性（P〈0.05）。结论：EGFR过度表达，在老年大肠癌的发生过程中可能起重要作用；检测EGFR对于指导临床治疗和判断预后有重要意义。     

造血干细胞移植患儿口腔黏膜炎风险预测模型的构建及验证

目的 分析造血干细胞移植患儿口腔黏膜炎的危险因素,构建风险预测模型,并验证其预测效果。方法采用便利抽样法,选取2019年1月—2022年6月于重庆市某三级甲等儿童专科医院行异基因造血干细胞移植的286例患儿作为调查对象,回顾性分析相关资料,通过Logistic回归分析筛选其口腔黏膜炎的危险因素,应用R 3.6.1软件绘制列线图,并进行验证。结果 Logistic回归分析结果显示,BMI<16、口腔pH值≤6.5、口腔清洁度评分为2～3分、预处理方案为减低强度或清髓性预处理、使用甲氨蝶呤、中性粒细胞计数<1.5×109/L是造血干细胞移植患儿口腔黏膜炎的危险因素（P<0.05）。Hosmer-Lemeshow检验结果提示,该风险预测模型具有较好的拟合度（χ2=0.969,P=0.998）。模型验证结果显示,该模型的受试者操作特征曲线下面积为0.881,最佳临界值为0.7,准确度为80.36%,灵敏度为83.59%,特异度为74.88%;预测口腔黏膜炎的一致性指数为0.881,校正一致性指数为0.862。结论 该研究构建的风险预测模型具有良好的区分度与准确度,可为临床护理...     

Management of radiation therapy-induced mucositis in head and neck cancer patients. Part II: supportive treatments

Oropharyngeal mucositis is the acute inflammatory and ulcerative reaction of the oral mucosa following radiation therapy to the head and neck region. It is such a common problem that nearly all head and neck cancer patients develop some degree of mucositis. This complication is usually transient in nature but it also represents an important clinical problem as it is a painful, debilitating, dose-dependent side effect for which there is no widely acceptable prophylaxis or effective treatment. As several authoritative groups have recently either undertaken systematic reviews or issued guidelines on the management of mucositis, it is the aim of this review instead, to provide an overview of all the remedies and pharmaceutical agents available, as well as highlighting to researchers the gaps that need to be filled.     

A randomized study of very accelerated radiotherapy with and without amifostine in head and neck squamous cell carcinoma

Purpose: The aim of this study was to assess whether amifostine could minimize acute mucositis induced by a very accelerated irradiation regimen in patients with advanced head and neck squamous cell carcinoma (HNSCC).

Methods and Materials: Between May 1996 and February 1998, 26 patients with an inoperable nonmetastatic Stage IV HNSCC were entered in this study. The treatment consisted of very accelerated radiotherapy given 64 Gy in 3.5 weeks. The patients were randomized to receive or not 150 mg/m², amifostine (Ethyol, U.S. Bioscience) 15–30 min prior to each radiation session.

Results: Of the 13 patients who received amifostine, definitive interruption of amifostine occurred in 5 cases (38%), due to tolerance problems (vomiting, liver enzyme elevation, generalized erythema). The distribution of Grade 4 mucositis (WHO) was 1 case versus 8 cases, with and without amifostine, respectively. The mean duration of “at least Grade 3” mucositis (WHO) was 25.1 days versus 49.2 days with and without amifostine (p = 0.03). In the amifostine group, 11/13 of the patients required a feeding tube (nasogastric tube or medical gastrostomy), because of acute mucositis, whereas in the control group a feeding tube was necessary in all cases. The mean duration of the use of this feeding tube was 1 month versus 2.5 months with and without amifostine respectively (p < 0.01). Local-regional control was not different between both arms with a median follow-up of 15 months.

Conclusion: Despite the limited number of patients, this pilot randomized study suggests that amifostine was able to markedly reduce the severity and duration of mucositis induced by very accelerated radiotherapy. However, the tolerance of this twice daily amifostine schedule was relatively poor.