X-radiation induces 8-hydroxy-2'-deoxyguanosine formation in vivo in rat mammary gland DNA

Ionizing radiation is a carcinogen that induces oxidative DNA damage. 8- Hydroxy-2'-deoxyguanosine (8-OHdG) is a relatively abundant, mutagenic lesion that is widely regarded as a reliable index of oxidative DNA damage. The purpose of this study was to examine the effects of X- radiation on levels of 8-OHdG in the context of an experimental model for breast cancer in which chronic radiation exposure has been shown to be carcinogenic in Sprague-Dawley rats. A secondary objective of this study was to determine if the use of phenol during DNA isolation affected the concentration of 8-OHdG subsequently measured. Our results indicate that a profoundly carcinogenic dose of radiation induced a small but significant increase in 8-OHdG concentration in mammary gland DNA, and that the use of a phenol-based versus a salt-based method of DNA isolation had no significant impact on the levels of 8-OHdG detected in either control or irradiated tissue.      

Effects of dietary fat and a vegetable-fruit mixture on the development of intestinal neoplasia in the ApcMin mouse

The variation in colorectal cancer (CRC) incidence worldwide strongly suggests a role for dietary influences. Based on epidemiological data, protective effects of vegetables and fruit intake on CRC are widely claimed, while other data indicate a possible increased CRC risk from (higher) dietary fat intake. Therefore, we have investigated single and interactive effects of dietary fat and a vegetable-fruit mixture (VFM) in the ApcMin mouse, a mouse model for multiple intestinal neoplasia. In this study, four different diets (A-D) were compared, which were either low in fat (20% energy diets A/B) or high in fat (40% energy diets C/D). In addition, 19.5% (wt/wt) of the carbohydrates in diets B and D were replaced by a freeze-dried VFM. The diets were balanced so that they only differed among each other in fat/carbohydrate content and the presence of specific plant-constituents. Because the initiation of intestinal tumors in ApcMin mice occurs relatively early in life, exposure to the diets was started in utero. Without the addition of VFM, mice maintained at a high-fat diet did not develop significantly higher numbers of small or large intestinal adenomas than mice maintained at a low-fat diet. VFM added to a low-fat diet significantly lowered multiplicity of small intestinal polyps (from 16.2 to 10.2/mouse, 15 animals/group), but not of colon tumors in male ApcMin mice only. Strikingly, addition of VFM to female mice maintained on a low-fat diet and to both sexes maintained on a high-fat diet significantly enhanced intestinal polyp multiplicity (from 16.5 to 26.7 polyps/mouse). In conclusion, our results indicate that neither a lower fat intake nor consumption of VFM included in a high-fat diet decreases the development of polyps in mice genetically predisposed to intestinal tumor development.      

Socioeconomic status and prevalence of allergic rhinitis and atopic eczema symptoms in young adolescents

Environmental factors are known to influence the development of allergic rhinitis and atopic eczema in genetically susceptible individuals. Socioeconomic status (SES) may be an important indicator of risk for these conditions. The International Study of Asthma and Allergies in Childhood (ISAAC) Phase 1 written questionnaire was used to determine the prevalence and severity of allergic rhinoconjunctivitis and atopic eczema symptoms in 4947 pupils aged 13-14 years attending 30 schools in socioeconomically diverse areas of Cape Town. Home addresses were used to stratify participants into five SES bands. Relationships between symptom prevalence and severity, and SES, recent urbanization and upward socioeconomic mobility were examined. Logistic regression was used to generate odds ratios (OR) and 95% confidence intervals (CI) in order to assess overall trends by SES. The prevalences of self-reported allergic rhinitis symptoms and recurrent itchy rash in the past year were 33.2% and 11.9% respectively. Girls had a significantly higher prevalence of all symptoms than boys. The prevalence of allergic rhinitis symptoms increased from lowest to highest SES (overall OR for rhinitis symptoms in past year = 1.16, 95% CI 1.11-1.21). There was no significant trend in reported eczema symptoms by SES other than for the question, 'Have you ever had eczema' (OR = 0.88, 95% CI 0.83-0.93). Longer period of urbanization was weakly associated only with recurrent itchy skin rash (OR = 1.05, 95% CI 1.01-1.09). 'Socially mobile' pupils, i.e. those resident in the lowest SES areas but attending highest SES schools showed significantly higher prevalences of eczema and some rhinitis symptoms than pupils attending lowest SES schools. These findings may reflect differences in reporting related to language, culture and access to medical care rather than real differences in prevalence.     

Insights into pediatric rhabdomyosarcoma research: Challenges and goals

Overall survival rates for pediatric patients with high‐risk or relapsed rhabdomyosarcoma (RMS) have not improved significantly since the 1980s. Recent studies have identified a number of targetable vulnerabilities in RMS, but these discoveries have infrequently translated into clinical trials. We propose streamlining the process by which agents are selected for clinical evaluation in RMS. We believe that strong consideration should be given to the development of combination therapies that add biologically targeted agents to conventional cytotoxic drugs. One example of this type of combination is the addition of the WEE1 inhibitor AZD1775 to the conventional cytotoxic chemotherapeutics, vincristine and irinotecan.     

Ileal dysgenesis coexisting with multiple enteric duplication cysts in a child—MR enterography, CT, and Meckel scan appearances

There are numerous causes of iron deficiency anemia due to gastrointestinal tract bleeding in children. While a very thorough history may elucidate common etiologies, such as cow’s milk protein-induced colitis and nonsteroidal anti-inflammatory drug-related gastritis or peptic ulcer disease, other less frequent causes often present a diagnostic challenge. We present the MR enterography (MRE), CT and Meckel scan findings of ileal dysgenesis coexisting with multiple enteric duplication cysts in a young child who presented with chronic iron deficiency anemia, recurrent gastrointestinal tract bleeding and unexplained bowel perforation. In this case, MRE was able to identify and characterize each individual lesion and directly guide appropriate surgical management.