Immersive virtual reality in orthopedic surgery as elective subject for medical students : First experiences in curricular teaching.

BACKGROUND: Virtual reality (VR) simulators have been introduced for skills training in various medical disciplines to create an approximately realistic environment without the risk of patient harm and have improved to more immersive VR (iVR) simulators at affordable costs. There is evidence that training on VR simulators improves technical skills but its use in orthopedic training programs and especially in curricular teaching sessions for medical students are currently not well established. The aim of this study was to describe the implementation of a VR operating theater as an elective course for undergraduate medical students and to evaluate its effect on student learning. METHODS: An elective course for 12 students was implemented during the summer semester of 2023. Using Oculus Quest 2 headsets (Reality Labs, Meta Platforms, USA) and controllers and the PrecisionOS platform, they were able to train five different surgical procedures. The courses were accompanied by weekly topic discussions and instructional videos. Students were assigned to two groups: group VR vs. group non-VR. The groups were switched after 5 weeks. User feedback and performance development (theoretical and procedural surgical knowledge) after VR training were assessed using three questionnaires. RESULTS: The students highly appreciated the implementation of VR training into their curriculum and 91% stated that they would opt for further VR training. All students stated that VR training improved their understanding of surgical procedures and that it should be obligatory in surgical training for undergraduate medical students. After 5 weeks of training, students in the VR group achieved significantly better results (100 out of maximum 180 points) than the non-VR group (70 points, p = 0.0495) in procedural surgical knowledge. After completion of the VR training the VR group achieved 106 points and the non-VR group 104 points (p = 0.8564). The procedural knowledge for non-VR group after 5 weeks significantly improved after VR training from 70 to 106 points (p = 0.0087). CONCLUSION: The iVR can be easily integrated into the curriculum of medical students and is highly appreciated by the participants. The iVR statistically improves the procedural knowledge of surgical steps compared to conventional teaching methods. Further implementation of iVR training in curricular teaching of medical students should be considered.

Interteam PERINAT - interprofessional team collaboration in undergraduate midwifery and medical education in the context of obstetric emergencies: Presentation of simulation scenarios and empirical evaluation results.

To promote the expansion of interprofessional training objectives in the curriculum of health professions curriculum at the Medical Faculty, University of Leipzig, the interprofessional teaching project between the Department of Obstetrics, the Skills and Simulation Centre and the School of Midwifery was selected to promote innovative teaching projects, supported by the University of Leipzig [https://www.stil.uni-leipzig.de/] grant "StiL - Studying in Leipzig". Using scenarios with simulated patients, students were to recall and apply theoretically learned procedures and immediate measures in an obstetric emergency under supervision and to communicate these clearly in the team. Final-year medical students from the Medical Faculty (n=15) and midwifery students (n=17) from the vocational school went through teaching situations together, in which two simulation scenarios (shoulder dystocia and postpartum haemorrhage) were implemented. The aim of the project was to integrate interprofessional collaboration into training and to learn together under simulated conditions in the Skills and Simulation Center protected environment. The following questions was intended to be clarified in the project in addition to the establishment of a sub-professional teaching unit What do students benefit most from in interprofessional teaching units? Are there differences between midwifery and medical students? Is the learning success the same for team-communicative and professional learning goals? To clarify the questions, an evaluation was carried out using an exploratory questionnaire with a Likert scale. All students particularly liked the exchange and contact with other professional groups, the communicative aspect and situational action in unforeseen emergency situations. The participants stated that they had benefited from both interprofessional teaching units, in terms of team communication as well as in professional terms. However, medical students experienced significantly higher cognitive overload regarding prior acquired knowledge compared to vocational midwifery students. Overall, the team communication learning objectives were more difficult to fulfill.

Deaf awareness workshop for medical students - an evaluation.

Background: Due to a lack of communication strategies and knowledge about the Deaf community, health care professionals are often not prepared to provide deaf or hard of hearing patients with accessible and adapted healthcare. Methods: In the present study, a workshop was designed to determine the effect of deaf awareness training on medical students concerning their gain of knowledge regarding deafness and their competence in providing adapted communication and healthcare for deaf and hard of hearing patients. 95 medical students were evaluated in an online survey prior to as well as following the workshop. The workshop was held online in three consecutive sessions. Results: Students reported a substantially more confident approach to working with hearing impaired patients and indicated that an online learning environment is a suitable and helpful alternative to face-to-face teaching. Participants improved significantly in all evaluated items concerning their knowledge and competence (p<0.001). Furthermore, measurements revealed interaction effects between students' current period of study and the point in time of self-evaluation before and after the workshop. Preclinical students not only catch up but even surpass their clinical peers concerning their learning outcome. Conclusion: Reviewing the results obtained by this study, we are optimistic with respect to all participants' highly positive experiences and learning outcomes. Deaf awareness training should be included in the curriculum of all medical faculties.

Evaluating the effectiveness of a structured, simulator-assisted, peer-led training on cardiovascular physical examination in third-year medical students: a prospective, randomized, controlled trial.

Background: Previous research suggests that cardiac examination skills in undergraduate medical students frequently need improvement. There are different ways to enhance physical examination (PE) skills such as simulator-based training or peer-assisted learning (PAL). Aim: The aim of this study was to evaluate the effectiveness of a structured, simulator-assisted, peer-led training on cardiovascular PE. Methods: Participants were third-year medical students at Leipzig University Faculty of Medicine. Students were randomly assigned to an intervention group (IG) and a control group (CG). In addition to standard curricular training, IG received a peer-led, simulator-based training in cardiac PE. Participant performance in cardiac PE was assessed using a standardized checklist with a maximum of 25 points. Primary outcome was assessed via checklist point distribution. Results: 89 students were randomised to either CG (n=43) or IG (n=46) with 70 completing the study. Overall, IG students performed significantly better than CG students did (max. points: 25, M±SD in IG was 17±3, in CG 12±4, p<.0001). Simple mistakes such as not using the stethoscope correctly were more frequent in CG students. Prior experience did not lead to a significant difference in performance. Conclusions: Structured, peer-led and simulator-assisted teaching sessions improve cardiac PE skills in this setting compared to control students that did not receive this training.

The Longitudinal Communication Curriculum at Leipzig University, Medical Faculty - implementation and first experiences.

Purpose: Communication skills are an essential instrument for building a sustainable patient-doctor-relationship for future doctors. They are learnable and teachable. The learning should be facilitated with the help of a longitudinal curriculum, which is planned at Leipzig University. Project: At the Medical Faculty of Leipzig University, the Longitudinal Communication Curriculum is established since 2016/17. Up to now, the curriculum consists of four parts in which students repeatedly practise their communication skills in curricular and extracurricular courses. Several formats help to teach an integrated learning of communication and physical examination skills. Assessment of communication skills is also performed. Curricular implementation is accompanied by concomitant evaluation. Results: Three parts of the curriculum already have taken place. Students report an increase in communication skills. Students rate the units as instructive and helpful. The assessment of communication skills occurs in two clinical practical examinations (OSCEs). Together with summative assessment a formative feedback was implemented. Students judge this practice as highly positive. Discussion: The curriculum is part of undergraduate medical education in Leipzig. It would be beneficial to add another simulated patient encounter, as well as interprofessional units. Student questionnaires will be evaluated and results will help to develop the curriculum. Conclusion: Consolidation of the curriculum accompanied by evaluation and adaption of content can help to assure the quality of the curriculum. Additional professions and study units shall be integrated in the Longitudinal Communication Curriculum in the future.

Evaluation of an educational concept for risk-oriented prevention in undergraduate dental education.

BACKGROUND: Aim of this observational study with a three-month follow-up was to evaluate an educational concept for risk-oriented prevention applied by fifth-year undergraduate dental students. METHODS: Dental students from two clinical treatment courses of the last undergraduate year were included. The subjects were divided into two groups according to their assignment to the two clinical classes. Group A received a sequence of seminars, including the basics of a risk classification system (RCS) with the theoretical background and case studies in the context of preventive dentistry. Thereby, 1) a theoretical seminar (background, RCS, cases) and 2) the transfer of the RCS on a clinical patient case chosen by the student, and its presentation within a discussion round was applied. Group B served as a comparison group with students who did not receive any of teaching events in terms of RCS. The self-perceived knowledge and importance of RCS, as well as objective knowledge (qualitative questions), were assessed with a standardized questionnaire at baseline and after 3 months. RESULTS: Out of 90 students at baseline, 79 (group A: 39, group B: 40) were re-evaluated after 3 months. At this follow-up, Group A estimated their confidence in handling the medication (p = 0.02), the RCS (p < 0.01), and in identifying the risk of oral diseases (p = 0.02) higher than group B. Furthermore, group A felt it was more important to identify patients at risk (p = 0.02), the risk of complications (p = 0.02) and to apply an RCS (p = 0.03). At follow-up, group A exhibited more correct answers of qualitative questions than group B regarding risk of complications (p < 0.01) and bacteremia (p < 0.01). Group A felt more confident with at-risk patients and more competent concerning RCS than group B (p < 0.01). CONCLUSION: The concept for educating risk-oriented prevention increased the self-perceived skills and the knowledge of undergraduate dental students after 3 months within a clinical treatment course.

Impact of simulator-based training on acquisition of transthoracic echocardiography skills in medical students.

Introduction: Due to the expanding role of ultrasound as a diagnostic tool in modern medicine, medical schools rapidly include ultrasound training in their curriculum. The objective of this study was to compare simulator-based training along with classical teaching, using human models, to impart focused transthoracic echocardiography examination. Subject and Methods: A total of 22 medical students, with no former transthoracic echocardiography training, undertook a 90-min e-learning module, dealing with focused echocardiography and important echocardiographic pathologies. Subsequently, they had to complete a multiple-choice-questioner, followed by a 120-min practical training session either on the Heartworks™, (Cardiff, UK) and the CAE Vimedix®, (Québec, Canada) simulator (n = 10) or on a live human model (n = 12). Finally, both groups had to complete a post-test consisting of ten video-based multiple-choice-questions and a time-based, focused echocardiography examination on another human model. Two blinded expert observers scored each acquired loop which recorded 2 s of each standard view. Statistical analysis was performed with SPPS 24 (SPSS™ 24, IBM, USA) using the Mann-Whitney-Test to compare both groups. Results: Analysis of measurable outcome skills showed no significant difference between transthoracic echocardiography training on human models and high-fidelity simulators for undergraduate medical students. Conclusions: Both teaching methods are effective and lead to the intended level of knowledge and skills.

Undergraduate ultrasound education at German-speaking medical faculties: a survey.

Background: The purpose of this study was twofold: to assess the status of undergraduate medical ultrasound (US) education in the German-speaking area and to suggest a possible framework for a longitudinal undergraduate medical US curriculum based on the study results and a literature review. Methods: The survey included 44 medical faculties in the German-speaking area: 37 in Germany, four in Austria and three in German-speaking Switzerland. A standardized questionnaire focused on the following aspects of undergraduate medical US education: general information, organization, resources, assessment methods and evaluation. Results: Data from 28 medical faculties were analysed. 26 out of 28 medical faculties offered US courses, 21 offered compulsory as well as elective courses, four offered compulsory and one elective courses only. 27 medical faculties supported US skills implementation. Abdominal US (n=25) was most common in teaching basic US skills. A learning objective catalogue was provided at 15 medical faculties. At 22 medical faculties, medical specialists were involved in undergraduate medical US education. 24 out of 26 medical faculties thought that peer-teaching is important to convey US skills. Medical faculties used the following methods to assess US skills: objective structured clinical examination (OSCE, n=7), non-standardized practical exams (n=4), non-standardized combined oral-practical exams (n=2) or direct observation of procedural skills (DOPS, n=1). 25 out of 26 medical faculties evaluated their US courses and 19 made suggestions for improvements in undergraduate medical US education. Conclusion: Medical faculty members in the German-speaking area have recognized the relevance of undergraduate medical US education. So far, courses are offered heterogeneously with rather short hands-on scanning time and high student-instructor ratio. Based on the results of this study and a literature review we suggest a possible framework and milestones on the way to a longitudinal undergraduate medical US curriculum.

Impact of Quantitative Feedback via High-Fidelity Airway Management Training on Success Rate in Endotracheal Intubation in Undergraduate Medical Students-A Prospective Single-Center Study.

Endotracheal intubation is still the gold standard in airway management. For medical students and young professionals, it is often difficult to train personal skills. We tested a high-fidelity simulator with an additional quantitative feedback integration to elucidate if competence acquisition for airway management is increased by using this feedback method. In the prospective trial, all participants (n = 299; 4th-year medical students) were randomized into two groups-One had been trained on the simulator with additional quantitative feedback (n = 149) and one without (n = 150). Three simulator measurements were considered as quality criteria-The pressure on the upper front row of teeth, the correct pressure point of the laryngoscope spatula and the correct depth for the fixation of the tube. There were a total of three measurement time points-One after initial training (with additional capture of cognitive load), one during the exam, and a final during the follow-up, approximately 20 weeks after the initial training. Regarding the three quality criteria, there was only one significant difference, with an advantage for the control group with respect to the correct pressure point of the laryngoscope spatula at the time of the follow-up (p = 0.011). After the training session, the cognitive load was significantly higher in the intervention group (p = 0.008) and increased in both groups over time. The additional quantitative feedback of the airway management trainer brings no measurable advantage in training for endotracheal intubation. Due to the increased cognitive load during the training, simple airway management task training may be more efficient for the primary acquisition of essential procedural steps.

International Peer-teaching: the LernKlinik Leipzig "Erasmus-Week" for Incoming Erasmus Students.

Introduction: This project report describes the development, pilot phase, evaluation and implementation of a preparatory course week for incoming Erasmus medical students at the LernKlinik Leipzig, the Skills and Simulation Centre of the Medical Faculty, University of Leipzig. Project description: The aim of this project is to prepare Erasmus students for their year abroad using peer-assisted teaching as the method of choice. Major intended outcomes were support of language and clinical practical skill competency development, as well as enhancement of integration among international and German-speaking peer tutors. The methodological framework of Ross and Cameron [1] was used in planning the Erasmus-Week. For planning the 2012 pilot project, a survey among Erasmus students of the academic year 2011/12 was performed. All succeeding cohorts were asked to participate in pre- and post-surveys which were analyzed quantitatively and qualitatively. Results: Between 2012 and 2017, n=173 European medical students spent their Erasmus year in Leipzig. Of these, n=148 (86%) participated in the Erasmus-Week. The country of origin of most Erasmus students was Rumania (20,3%). Among the most positively received aspects of the Erasmus-Week, the active use of German for medical purposes and the use of peer-teaching as the method of choice to learn and repeat basic medical examination skills were mentioned. Students emphasized their wish for being able to participate in further course offers. Conclusions: Offering a preparatory course week for incoming Erasmus students focusing on language and clinical practical skills training using peer-teaching as the method of choice may facilitate the integration of Erasmus students into their foreign medical curriculum. Further studies are underway to elucidate if these experiences influence later professional careers and choice of employment.

[Clinical-practical Examination in Orthopaedic Teaching: Who is the "Ideal" Examiner?] / Klinisch-praktische Prüfungen in der orthopädischen Lehre: Wer ist der "ideale" Prüfer?

Background Medical curricula require an increasing amount of integrated clinical practical skills education. German medical faculties are increasingly implementing the OSCE (objective structured clinical examination) to test students' practical as well as communication skills. Teaching and assessment tools for practical skills include simulators and simulated patient scenarios, where peer-assisted teaching (PAT) is applied. Trained student tutors support this process. This study examines for the first time the use of PAT student tutors as examiners in an orthopaedic OSCE unit and the existence of possible differences in rating between faculty and PAT student tutors. Material and Methods N = 94 students (out of n = 324) in their first clinical year were randomly assigned to the OSCE unit "spine and pelvis examination" in March/April 2016 and data were collected over the three-day OSCE period. A structured checklist was developed and the two examiners (one university professor from the Department of Orthopaedics, one PAT student tutor) received identical preparatory training. The checklist was completed by both examiners independently and data were collected for statistical analysis. The analysis focused on the overall evaluation in points, as well as separate checklist sections focusing on different competences and comparison of the three consecutive examination days. Analysis was conducted by SPSS. Results The average number of points in the overall evaluation was 19.5 (out of 25) points. The student tutor evaluated the students with an average of 19.1 points, the professor with 19.9 points. A significant difference was observed between the two examiner evaluations of day one (p < 0.001) and in the overall analysis (p < 0.001). On OSCE examination days 2 and 3, no significant differences in evaluation were observed. Conclusion The analysis shows only one significant evaluation difference between the two assessors, with the PAT student tutor's evaluation being stricter. The authors conclude that a point difference of 0.8 out of 25 in the average overall evaluation and an interrater reliability of 0.95 in an orthopaedic OSCE station examining practical skills as well as communication skills justifies employing PAT student tutors as assessors in this context. The obligatory requirements for this are a detailed PAT student tutor training, the development of a well-structured and valid checklist, as well as continuous quality assurance of the overall OSCE.

Alpha tocopherol transfer protein (αTTP) is expressed in endometrial carcinoma and is correlated with FIGO stage and 5-year survival.

BACKGROUND: Increased oxidative stress plays an important role in cancer development. Vitamin E is considered a potent anti-oxidant and its transfer protein αTTP facilitates its cellular delivery. We hypothesize that αTTP could be present in and have an impact on endometrial cancer. MATERIALS AND METHODS: Ishikawa endometrial cancer cells were treated with BSO and AAPH to mimick oxidative stress conditions. αTTP was detected by immunocytochemistry and western blot. αΤΤP expression was then assessed in 191 endometrioid endometrial carcinomas. Immunopositivity was correlated with grade, FIGO stage, and 5-year survival. Immuno-reactivity was assessed with a semi-quantitative score. RESULTS: AAPH- and BSO-induced αTTP expression in Ishikawa cells. Immunohistochemical assessment of the 191 endometrial cancer cases showed that αTTP expression correlated with FIGO stage (p = 0.014) but not with grade. Five-year survival was significantly better in cases of lower αTTP expression compared to cases with higher expression (p = 0.041). CONCLUSIONS: The current results show that αTTP plays a role in endometrial carcinoma. Possibly endometrial cancer cells attempt to protect themselves from increasing oxidative stress by up-regulating αTTP. Selective molecular interventions targeting oxidative stress escape strategies, e.g., by overexpression of αTTP, could, therefore, allow oxidative stress to damage cancer cell membranes and thus restrict cancer progression.

Students benefit from developing their own emergency medicine OSCE stations: a comparative study using the matched-pair method.

BACKGROUND: Students can improve the learning process by developing their own multiple choice questions. If a similar effect occurred when creating OSCE (objective structured clinical examination) stations by themselves it could be beneficial to involve them in the development of OSCE stations. This study investigates the effect of students developing emergency medicine OSCE stations on their test performance. METHOD: In the 2011/12 winter semester, an emergency medicine OSCE was held for the first time at the Faculty of Medicine at the University of Leipzig. When preparing for the OSCE, 13 students (the intervention group) developed and tested emergency medicine examination stations as a learning experience. Their subsequent OSCE performance was compared to that of 13 other students (the control group), who were parallelized in terms of age, gender, semester and level of previous knowledge using the matched-pair method. In addition, both groups were compared to 20 students who tested the OSCE prior to regular emergency medicine training (test OSCE group). RESULTS: There were no differences between the three groups regarding age (24.3 ± 2.6; 24.2 ± 3.4 and 24 ± 2.3 years) or previous knowledge (29.3 ± 3.4; 29.3 ± 3.2 and 28.9 ± 4.7 points in the multiple choice [MC] exam in emergency medicine). Merely the gender distribution differed (8 female and 5 male students in the intervention and control group vs. 3 males and 17 females in the test OSCE group).In the exam OSCE, participants in the intervention group scored 233.4 ± 6.3 points (mean ± SD) compared to 223.8 ± 9.2 points (p < 0.01) in the control group. Cohen's effect size was d = 1.24. The students of the test OSCE group scored 223.2 ± 13.4 points. CONCLUSIONS: Students who actively develop OSCE stations when preparing for an emergency medicine OSCE achieve better exam results.

Study of medicine 2.0 due to Web 2.0?! -- risks and opportunities for the curriculum in Leipzig.

Web 2.0 is changing the study of medicine by opening up totally new ways of learning and teaching in an ongoing process. Global social networking services like Facebook, YouTube, Flickr, Google Drive and Xing already play an important part in communication both among students and between students and teaching staff. Moreover, local portals (such as the platform [http://www.leipzig-medizin.de] established in 2003) have also caught on and in some cases eclipsed the use of the well-known location-independent social media. The many possibilities and rapid changes brought about by social networks need to be publicized within medical faculties. Therefore, an E-learning and New Media Working Group was set up at the Faculty of Medicine of Universität Leipzig in order to harness the opportunities of Web 2.0, analyse the resulting processes of change in the study of medicine, and curb the risks of the Internet. With Web 2.0 and the social web already influencing the study of medicine, the opportunities of the Internet now need to be utilized to improve the teaching of medicine.

Oxidative stress stimulates α-tocopherol transfer protein in human trophoblast tumor cells BeWo.

α-Tocopherol transfer protein (α-TTP) has been identified as the major intracellular transport protein for the antioxidant vitamin E (α-tocopherol). Expression of α-TTP on the reproductive system has been described both in mouse uterus and lately in the human placenta. The aim of this study was to clarify if placental expression of α-TTP can be modified by substances causing oxidative reactions. The human choriocarcinoma cell line BeWo was, therefore, treated with two known pro-oxidants. α-TTP expression was determined with immunocytochemistry and evaluated by applying a semiquantitative score. The presence of pro-oxidants in BeWo cells induced α-TTP expression. We thus hypothesize that stimulation of α-TTP expression by oxidative stress, as this was induced by pro-oxidants, could be part of an antioxidant process occurring in the placenta in the aim of enhancing the supply of α-tocopherol. This process could occur both in normal pregnancies, as well as in pregnancy disorders presented with intensified oxidative stress. In that view, this model is proposed for further oxidative stress studies on trophoblast and placenta, on the grounds of clarifying the role of α-tocopherol in pregnancy physiology and pathophysiology.

A novel role for α-tocopherol transfer protein (α-TTP) in protecting against chloroquine toxicity.

Chloroquine (CQ) is a widely prescribed anti-malarial agent and is also prescribed to treat autoimmune diseases. Clinical treatment with CQ is often accompanied by serious side effects such as hepatitis and retinopathy. As a weak base, CQ accumulates in intracellular acidic organelles, raises the pH, and induces osmotic swelling and permeabilization of acidic organelles, which account for CQ-induced cytotoxicity. We reported previously that CQ treatment caused α-tocopherol transfer protein (α-TTP), a gene product of familial vitamin E deficiency, to change its location from the cytosol to the surface of acidic organelles. Here we show that α-TTP plays a novel role in protecting against CQ toxicity both in vitro and in vivo. In the presence of CQ, rat hepatoma McARH7777 cells, which do not express α-TTP endogenously, showed more severe cytotoxicity, such as larger vacuolation of acidic organelles and caspase activation, than α-TTP transfectant cells. Similarly, α-TTP knockout mice showed more severe CQ toxicity, such as hepatotoxicity and retinopathy, than wild-type mice. These effects were not ameliorated by vitamin E supplementation. In contrast to bafilomycin A1 treatment, which prevents CQ accumulation in cells by raising the pH of acidic organelles, α-TTP expression prevented CQ accumulation without affecting the pH of acidic organelles. Taken together, our data suggest that α-TTP protects against CQ toxicity by preventing CQ accumulation in acidic organelles through a mechanism distinct from vitamin E transport.

ATP-binding cassette transporter A1 is involved in hepatic alpha-tocopherol secretion.

Vitamin E (alpha-tocopherol) is an essential fat-soluble nutrient with antioxidant properties. alpha-Tocopherol transfer protein (alpha-TTP), the product of the gene responsible for familial isolated vitamin E deficiency, plays an important role in maintaining the plasma alpha-tocopherol level by mediating the secretion of alpha-tocopherol by the liver. However, the mechanisms underlying hepatic alpha-tocopherol secretion are not fully understood. This study was undertaken to elucidate the mechanism of alpha-tocopherol re-efflux from hepatocytes, the cells that have the most important role in regulating plasma-alpha-tocopherol concentrations. From in vitro experiments using [(3)H]alpha-tocopheryl acetate and McARH7777 cells that stably express alpha-tocopherol transfer protein (alpha-TTP), the following results were obtained. First, addition of apolipoprotein A-I (apoA-I), a direct acceptor of the ATP-binding cassette transporter A1 (ABCA1)-secreted lipids, increased alpha-tocopherol secretion in a dose-dependent manner. Second, probucol, an antiatherogenic compound reported to be an inactivator of ABCA1 reduced hepatic alpha-tocopherol secretion. Third, ABCA1-RNAi suppressed hepatic alpha-tocopherol secretion. In a mouse in vivo experiment, addition of 1% probucol to the diet decreased plasma alpha-tocopherol concentrations. These results strongly suggest that ABCA1 is substantially involved in hepatic alpha-tocopherol secretion.

Immunohistochemical localization of alpha-tocopherol transfer protein and lipoperoxidation products in human first-trimester and term placenta.

OBJECTIVE: Pregnancy is described as a state of oxidative stress arising from the high metabolic turnover taking place during feto-placental development and little is known about the balance of oxidation and antioxidation in early human pregnancy. The aim of this study was to analyze placental expression of alpha-tocopherol transfer protein (alpha-TTP) as the major transport protein for the antioxidant alpha-tocopherol as well as the placental expression of two lipoperoxidation products, malondialdehyde (MDA) and 4-hydroxy-2-nonenal (HNE) in early first-trimester and term human placenta. STUDY DESIGN: Placental tissue was obtained from 10 pregnancy interruptions at 6-8 weeks gestational age and 10 samples were obtained from term pregnancies after routine cesarean section. The placental expression of alpha-TTP, MDA and HNE has been investigated with immunohistochemistry by the use of specific human alpha-TTP, MDA and HNE antibodies. RESULTS: While MDA and HNE showed similar expression in first-trimester and term placenta, alpha-TTP expression was less in first-trimester syncytiotrophoblast as compared to term. In first-trimester specimen, alpha-TTP showed major expression in extravillous trophoblast. In amniotic epithelial cells, a rising tendency in all three parameters investigated from immature to mature cells could be documented. No direct correlation between alpha-TTP, MDA and HNE expression was detected. CONCLUSIONS: Our study shows the presence of alpha-TTP not only in term, but in first-trimester extravillous trophoblast, syncytiotrophoblast and amniotic epithelium. Furthermore, lipoperoxidation products MDA and HNE are also present in first-trimester and term placenta, documenting the presence of oxidative processes in the placenta from early on. It therefore seems possible that scavenging of reactive oxygen species (ROS) by alpha-tocopherol is already required in first-trimester human pregnancy, but the missing correlation to MDA and HNE expression leads to the speculation that alpha-TTP and its ligand alpha-tocopherol have functions beyond the antioxidative capacity of alpha-tocopherol in early pregnancy.

Influence of long-chain polyunsaturated fatty acid formula feeds on vitamin E status in preterm infants.

It has been recommended to supplement formulas for preterm infants with n-3 and n-6 long-chain polyunsaturated fatty acids (LCP) to improve growth, visual acuity, and neurodevelopmental performance. However, large amounts of LCP may increase lipid peroxidation and oxidative stress in preterm infants. We investigated if, under high supplementation of natural tocopherols, LCP addition to formula can be performed safely without causing tocopherol depletion in cell membranes. Thirty-one healthy preterm infants with gestational ages from 28 to 32 weeks were evaluated in a prospective, randomized study from birth to day 42. Nine infants received an n-3 and n-6 LCP-enriched formula (A), eleven infants a standard formula (B), and eleven infants breast milk (control group). Alpha- and gamma-tocopherol extracts were added to both formulas, amounting to five times the value in breast milk (2.3 mg/dL in both formulas versus 0.45 mg/dL in breast milk). Erythrocyte arachidonic acid (AA) and docosahexaenoic acid (DHA) in the phosphatidylethanolamine fraction were similar in the three groups over the study period, whereas a significant reduction of erythrocyte AA and DHA could be detected in the phosphatidylcholine fraction in all three groups from day 14 onwards, when compared to respective cord blood values, with lowest values in the standard formula group. Amazingly, levels of alpha- and gamma-tocopherol were higher in plasma, erythrocytes, platelets, monocytes, and polymorphonuclear leukocytes with LCP supplementation as compared to standard formula and breast milk from day 7 onwards, whereas in buccal mucosal cells, this was not the case until day 42. Gammatocopherol uptake in the LCP-supplemented group was also significantly higher in all cell fractions studied from day 7 onwards. We therefore hypothesize that the LCP supplementation used in formula A improves tocopherol solubility and stability in biological membranes. Under high-dose vitamin E addition to n-3 and n-6 LCP-supplemented formula, no evidence for tocopherol depletion and furthermore, high accumulation of tocopherols, can be detected in healthy preterm infants.