The effect of non-genotoxic carcinogens, phenobarbital and clofibrate, on the relationship between reactive oxygen species, antioxidant enzyme expression and apoptosis

Phenobarbital and clofibrate, two non-genotoxic carcinogens, have been investigated regarding the relationship between reactive oxygen species, antioxidant enzyme expression and apoptosis in primary cultures of rat hepatocytes. Low toxicity concentrations, 200 and 100 microg/ml for phenobarbital and clofibrate respectively, were used to examine their effect on spontaneous or transforming growth factor beta1 (TGFbeta1)-induced apoptosis and on the expression of antioxidant defence enzymes (superoxide dismutases and catalase). The increased incidence of apoptotic nuclei was visualized in TGFbeta1-treated cultures with the fluorescent dye Hoechst 33258 and was quantified under all experimental conditions by measurement of the hypodiploid peak in DNA histograms obtained by flow cytometry. Both substances, when added separately to hepatocyte cultures and incubated for 24 and 48 h, significantly diminished spontaneous apoptosis and exhibited a slight suppression of TGFbeta1-induced apoptosis. Endogenous peroxide production by hepatocytes increased with TGFbeta1, phenobarbital or clofibrate and the increase was greater with phenobarbital and in the presence of TGFbeta1 with both drugs. Gene expression of catalase and Mn- and Cu,Zn superoxide dismutases (SOD) was evaluated by northern blot analysis of hepatocytes incubated in the presence of phenobarbital or clofibrate with or without TGFbeta1 and the following differences were detected: phenobarbital induced a significant decrease in both dismutases (to 56%, P < 0.05, and 55%, P < 0.05, for Mn- and Cu,Zn-SOD respectively) and a 2-fold increase (P < 0.01) in catalase; clofibrate induced a slight decrease in both SODs and a 4-fold increase (P < 0.05) in catalase; TGFbeta1 significantly decreased to 37% (P < 0.05) expression of catalase while not significantly affecting expression of both SODs. We conclude that inhibition of spontaneous apoptosis induced by either phenobarbital or clofibrate is accompanied by increases in the endogenous levels of peroxides and by significant induction of catalase gene expression. Furthermore, the lack of effect of both compounds on TGFbeta1-induced apoptosis could be a consequence of the inability of these two compounds to counteract the depressing effect of TGFbeta1 on expression of catalase.      

How well do third-year medical students learn key objectives in a case-based surgical lecture series?

Faculty members were asked to list major and minor concepts of their case-based session presented during the 12-week 3rd-year surgical clerkship. After each session, students were queried to list the key concepts presented. Data were collected from two groups: one at the end of an academic year and a second at the beginning of the next academic year. Faculty members listed a median of 10 major and 15 minor concepts. The mean number of matched major concepts ranged from 0.2 to 4, and from 0.2 to 3.4 for minor concepts. In a comparative analysis, the end-of-the-year students listed a higher number of matched concepts for 17 of the 20 sessions than the beginning of the year students (8 sessions reached statistical significance, P < 0.05). The current case-based teaching method is not effective in emphasizing key concepts to students. Reformatting cases to better align with key concepts may be one solution to enhance a student's ability to grasp key concepts. Students at the end of the academic year outperformed those at the beginning of the year. This additional variable needs to be considered by faculty and incorporated into their teaching techniques.     

Rendu–Osler–Weber syndrome presenting with pulmonary arteriovenous fistula

A pulmonary arteriovenous fistula is an abnormal connection between pulmonary arteries and veins. Patients with Rendu–Osler–Weber syndrome may present with this vascular malformation, which is a typical finding of the disease. Approximately 5–15% of Rendu–Osler–Weber syndrome patients have pulmonary arteriovenous malformations (AVM) and there is usually a family history of AVM in these patients. The malformations are usually located in the lower lobes. In this paper, I describe a 49‐year‐old male patient with dyspnoea, cough, haemoptysis and epistaxis. Physical examination showed nasal telangiectasias, cyanosis of the lips and nails, and a systolic bruit over the left lung. Chest X‐ray revealed a 5‐cm mass in the left lower lobe and after magnetic resonance examination, together with 3‐D magnetic resonance angiography, it was demonstrated to be a pulmonary arteriovenous fistula. The history of a niece with a similiar history of suspected pulmonary arteriovenous fistula led me to consider the possibility of Rendu–Osler–Weber syndrome presenting with a pulmonary arteriovenous fistula.     

Human patellar tendon strain. A noninvasive, in vivo study

This study showed the assumption of patellar tendon inextensibility was not valid, and the strain in the patellar tendon was higher than previously reported for other human tendons. The in vivo three-dimensional velocity profiles for the patella, femur, and tibia were measured noninvasively in 18 healthy knees during a low load extensor task using cine phase contrast magnetic resonance imaging. These data were used to calculate patellar tendon elongation and strain. Average maximum strains of 6.6% were found for a low load extension task at relatively small knee angles.     

Motivators and barriers to blood donation among potential donors of African and Caucasian ethnicity

BackgroundMinority blood donation, especially from individuals of African ethnicity, is a focus for many countries with diverse populations. As the need for antigen-negative RBC transfusions for patients with Sickle Cell Disease (SCD) continues to grow, inclusion of more African blood donors is essential to ensure this demand is met.Materials and methodsThis study aims to explore barriers and motivators to blood donation and awareness of SCD among potential donors of diverse ethnic backgrounds in Ireland. Following ethical approval, patients attending the National Sickle Cell Disease and Thalassemia service at St James’s Hospital were invited to share an online anonymous survey within their local communities to achieve snowball-sampling.Results387 respondents completed the survey, including 311 non-donors (median age 25 years, 67% female). Ethnic backgrounds included: African or African-Irish (59%), White or Caucasian (25%), Asian (8%), Hispanic or Latino (3%), Middle Eastern (3%), Multiracial or Biracial (2%). The most commonly identified barrier overall was lack of information on blood donation. African respondents were significantly more likely to report lack of information and malaria-related barriers than Caucasians. Motivators also varied across ethnic groups, with African respondents more likely to donate to help someone within their own community or for religious motivators. Awareness of SCD was higher among African respondents.DiscussionWhile some barriers to blood donation are shared across all ethnic groups including lack of information, notable differences exist between Caucasian and African respondents. Specific actions to recruit and retain African blood donors should focus on these key areas.