Subchronic mycotoxicoses in rats. Histopathological changes and modulation of the sphinganine to sphingosine (Sa/So) ratio imbalance induced by Fusarium verticillioides culture material, due to the coexistence of aflatoxin B1 in the diet.

Mycotoxicoses are diseases caused by consumption of diets contaminated with mycotoxins, a special class of fungal secondary metabolites. Fumonisin B1 (FB1) and aflatoxin B1 (AFB1), the main toxins synthesized by toxicogenic stocks of Fusarium spp. and Aspergillus spp., respectively, can coexist in grains and in its by-products. We investigated a probable synergism of a fumonisins-containing Fusarium verticillioides culture material and AFB1 in the induction of hepatocyte apoptosis in rats subchronically fed on a mixture of them. Furthermore, the possibility of modifications in the fumonisins-induced Sa/So ratio imbalance in tissues and urine from rats poisoned with this mycotoxin, due to the presence of AFB1 in the diet, was evaluated. The co-exposure to fumonisins and AFB1 produced a higher liver toxicity, with respect to their individual administration, inducing apoptosis and mitotic hepatocytes. There was an inversion of the typical Sa/So ratio in rats fed on the culture material as well as in those subjected to a diet co-contamined with fumonisins and AFB1. Moreover, the later had a synergistic effect in the induction of Sa/So variations in kidneys. Therefore, the mixture of fumonisins and AFB1 induced toxic responses which could not be considered a sum of the effects caused individually by these mycotoxins.     

大鼠肝癌形成过程MCM7基因动态变化

目的：4g讨MCM7基因在黄曲霉毒素B1（AFB1）实验诱发大鼠肝癌过程中的动态变化及意义。方法：将70只雄性4周龄Wistar大鼠随机分为AFB1组（50只）和对照组（20只）,AFB1组腹腔注射AFB1,对照纽则给予溶媒二甲基亚砜。在诱发肝癌过程中,分别于第13、33和53周对大鼠进行肝活检;实验至第73周处死全部大鼠取肝组织;采用实时荧光定量PCR、蛋白质印迹法和免疫组化方法检测肝组织中MCM7rnRNA和蛋白的表达情况。结果：AFB1组肝细胞癌发生率为44．1％（15／a4）,对照组为0（0／16）,AFB1组显著高于对照组,χ^2=8．093,P〈0．001。随着大鼠肝癌的形成,MCM7mRNA和蛋白的表达水平逐步升高,AFB1组第53和73周显著高于第13和33周,F值分别为55．632和207．253,P值均〈0．001;对照组各时间点的表达较低且变化不大。免疫组化结果显示,AFB1组第53周McM7蛋白阳性表达率为26．7％且以弱阳性为主,第73周MCM7蛋白阳性表达率为100％且多为强阳性,阳性表达率和表达强度均比其他时间点的高,两者比较差异均有统计学意义,P值均〈0．001。结论：MCM7表达水平随着肝癌的形成逐渐上升,且在肝癌组织中表达最高,MCM7有可能是参与肝癌形成的关键基因,但其详细机制有待进一步探讨。     

Molecular Mechanisms and Targets of Therapy for Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. HCC develops through a multistep process that involves the local tumor microenvironment, intracellular signaling pathways, and altered metabolic system that allows the cancer proliferation. Understanding the mechanisms of tumor development and progression is critical to developing improved therapies aimed at better survival. This article reviews the molecular mechanisms of HCC development and highlights the potential therapeutic targets for treatments.     

Low level aflatoxin exposure associated with greater linear growth in southern Mexico: A longitudinal study

Aflatoxins are a group of naturally occurring mycotoxins, which can lead to death and are a known cause of hepatocellular carcinoma. AF exposure has been hypothesised to lead to stunted growth in children, but separating the AF effect from other determinants of linear growth retardation is difficult. The study used secondary data from an efficacy trial conducted in young children in southern Mexico to test the comparative efficacy of a milk‐based multiple micronutrient‐fortified food, a multiple micronutrient syrup, or a multiple micronutrient powder. The effect of serum AFB₁‐lysine adduct level on incremental growth was tested using a longitudinal mixed model, controlling for key individual, maternal, and household‐level covariates. AFB₁‐lysine adduct was detectable in all but 2 of the 347 children in the study (median exposure: 0.82 pg/mg albumin). AF exposure was associated (p < .05) with greater linear growth: an increase equivalent to the sample interquartile range (~0.5 pg AFB₁‐lysine/mg albumin) was associated (p < .05) with an increase in the child's height‐for‐age deficit of 1.5 to 2.0 mm in the 4 months from baseline (average age 8 months) to follow‐up (average age 12 months); the magnitude of the difference in the 10‐month follow‐up was smaller and not statistically significant. This study documents that low‐dose AF exposure was associated with greater child linear growth. Given its toxicity and carcinogenicity, our results do not change the urgent need to drastically reduce human AF exposure. Our findings show that the association between AF exposure and linear growth is more complex than previously thought.     

Surgical management of the failed Nissen fundoplication

A significant percentage of surgery performed for complications of gastroesophageal reflux at a major medical center has been performed for problems related to prior surgery. Our patients who required remedial surgery fell into three categories. Those with recurrent reflux generally fared well. Patients with dysphagia, gastric stasis, or both presented difficult problems. The key to success for these patients lies in choosing the operation best suited to the anatomic and physiologic situation as defined by preoperative contrast studies, pH monitoring, endoscopy, and selective gastric emptying studies.     

Incorporation of [3H]uridine into RNA under the influence of dieldrin and polychlorinated biphenyls.

The present study was conducted to determine the influence of two organochlorines, i.e., polychlorinated biphenyl (Aroclor 1242) and dieldrin, or RNA synthesis in elicited peritoneal macrophages. Tritiated uridine ([³H]uridine) incorporation into RNA was used as an index of RNA synthesis. RNA synthesis was depressed in macrophages incubated in the presence of dieldrin in both a time- and dose-related manner. The dieldrin-induced inhibition of RNA synthesis was further exacerbated when the macrophages were actively phagocytosing latex particles. Aroclor 1242 similarly inhibited RNA synthesis in resting macrophages; however, inhibition was not seen until a concentration exceeding 7 ppm of Aroclor 1242 was used in the incubation medium. Dieldrin-induced inhibition of RNA synthesis was observed at levels of 1 ppm. The inhibition of RNA synthesis provides a corroborative index to support the hypothesis previously advanced that the observed in vivo organochlorine-induced immune suppression may be macrophage mediated. Since the observed in vivo immune suppression was manifested in the absence of any morphological changes in the target lymphoid-macrophage tissues, a biochemical lesion, perhaps at the level of RNA synthesis, may be a site for the organochlorine-induced immunosuppression.     

影响三地居民黄曲霉毒素B1-白蛋白加合物的相关因素分析

[目的]分析影响存在肝癌发病率梯度的三地居民个体黄曲霉毒素生物效应的相关因素.[方法]对广西扶挼两个自然村农民、南宁和四川成都城市居民采用酶联免疫法检测血浆黄曲霉毒素B1-白蛋白加合物(AFB1-Albumin Adducts,AAA)水平、肝炎病毒(hepatitis virus,HV)标志物(HBV两对半,HCV、HDV、HEV和HGV抗体)及肝功能.[结果]扶挼47.2%(42/89)的居民至少1种HV感染标志物阳性;南宁和成都分别为15.8%(31/196)和22.7%(27/119).Log(AAA)水平(n,x±s)为扶挼(89,2.44±0.16)和南宁(196,2.45±0.15)均高于成都(118,2.20±0.24),(P=0.000);但扶挼与南宁间差别无显著性(P=0.859).南宁(P=0.023)、成都(P=0.026)两地男性AAA水平均高于女性.扶挼和成都两地HV感染者AAA水平均高于非感染者(P分别为0.447和0.041).HV(-)组中,AAA水平与年龄(r=-0.199,P=0.000)和BMI(r=-0.158,P=0.006)负相关.HV(+)组AAA分别与白蛋白(P=0.000)、球蛋白(P=0.012)和天冬氨酸转氨酶(P=0.052)相关,而HV(-)组AAA分别与直接胆红素、间接胆红素、白蛋白、γ-谷氨酰转肽酶、总胆汁酸和碱性磷酸酶相关(P＜0.05).[结论]AFB1暴露的生物效应可能受肝炎病毒感染、性别、年龄和代谢等因素的影响.AAA与肝功能指标的相关性提示AFBl对肝脏实质或胆道细胞的损害作用.     

茯苓对AFB1致突变的抑制作用

本文以小鼠骨髓嗜多染红细胞微核和染色体畸变为指标，检测了中药茯苓对黄曲霉毒素Ｂ１致突变作用的影响，结果表明，茯苓煎剂对显著地抑制ＡＦＢ１的致突变作用（Ｐ〈０．０５）并呈量效关系。     

Cytologic diagnosis of tuberculous lymphadenitis in children by fine needle aspiration

One hundred consecutively diagnosed cases of tuberculous lymphadenitis in children have been analysed retrospectively. All cases were stained by May Grunwald Giemsa for cytomorphology and Ziehl Neelsen stain for acidfast bacilli (AFB). In 52 cases the material was sufficient and AFB cultures were possible. A diagnosis of tuberculosis was made when smears showed epithelioid cell granulomas or AFB on either smears or culture. M. tuberculosis and atypical mucobacteria were cultured in 26 and 3 cases respectively. In 6 cases the diganosis of tuberculosis would have been missed but for culture studies, the cytologic smears were necrotic and stains for AFB negative.