Feeding rats diets enriched in lowbush blueberries for six weeks decreases ischemia-induced brain damage

Oxidative stress is an important element in the etiology of ischemic stroke. Lowbush blueberries (Vaccinium angustifolium Aiton) have a high antioxidant capacity and thus we determined whether consumption of lowbush blueberries would protect neurons from stroke-induced damage. Rats were fed AIN-93G diets containing 0 or 14.3% blueberries (g fresh weight/100 g feed) for 6 weeks. Stroke was then simulated by ligation of the left common carotid artery (ischemia), followed by hypoxia. One week later, plasma and urine were collected, and neuronal damage in the hippocampus was determined histologically. In control rats, hypoxia-ischemia resulted in 40 +/- 2% loss of neurons in the hippocampus of the left cerebral hemisphere, as compared to the right hemisphere. Rats on blueberry-supplemented diets lost only 17 +/- 2% of neurons in the ischemic hippocampus. Neuroprotection was observed in the CA1 and CA2 regions, but not CA3 region, of the hippocampus. The blueberry diet had no detectable effects on the plasma or urine oxygen radical absorbance capacity (ORAC) or plasma lipids. We conclude that consumption of lowbush blueberries by rats confers protection to the brain against damage from ischemia, suggesting that inclusion of blueberries in the diet may improve ischemic stroke outcomes.     

Teaching and learning about bioscience ethics with undergraduates

Bioscience ethics acts as a practical interface between science and bioethics. It links scientific endeavour and its application into adaptive forms of bioethical consensus. Its major elements are increased understanding of biological systems, responsible use of technology, and curtailment of ethnocentric debates in tune with new scientific insights. This paper briefly describes the students' learning experience gained from the vacation unit BIOL 240, Introduction to Bioscience Ethics, as taught in biology, Macquarie University. On the basis of our evidence students were overwhelmingly positive about their learning because the unit assisted them to better face dilemmas that arise from the application of science and technology. The structure also provided active engagement with the subject matter and preferred learning environments that supported and contested their understanding of concepts relevant to bioscience and bioethics.     

Modified vaccinia virus ankara recombinants are as potent as vaccinia recombinants in diversified prime and boost vaccine regimens to elicit therapeutic antitumor responses

Cancer vaccine regimens use various strategies to enhance immune responses to specific tumor-associated antigens (TAAs), including the increasing use of recombinant poxviruses [vaccinia (rV) and fowlpox (rF)] for delivery of the TAA to the immune system. However, the use of replication competent vectors with the potential of adverse reactions have made attenuation a priority for next-generation vaccine strategies. Modified vaccinia Ankara (MVA) is a replication defective form of vaccinia virus. Here, we investigated the use of MVA encoding a tumor antigen gene, carcinoembryonic antigen (CEA), in addition to multiple costimulatory molecules (B7-1, intercellular adhesion molecule-1, and lymphocyte function-associated antigen-3 designated TRICOM). Vaccination of mice with MVA-CEA/TRICOM induced potent CD4+ and CD8+ T-cell responses specific for CEA. MVA-CEA/TRICOM could be administered twice in vaccinia na?ve mice and only a single time in vaccinia-immune mice before being inhibited by antivector-immune responses. The use of MVA-CEA/TRICOM in a diversified prime and boost vaccine regimen with rF-CEA/TRICOM, however, induced significantly greater levels of both CD4+ and CD8+ T-cell responses specific for CEA than that seen with rV-CEA/TRICOM prime and rF-CEA/TRICOM boost. In a self-antigen tumor model, the diversified MVA-CEA/TRICOM/rF-CEA/ TRICOM vaccination regimen resulted in a significant therapeutic antitumor response as measured by increased survival, when compared with the diversified prime and boost regimen, rV-CEA/TRICOM/rF-CEA/TRICOM. The studies reported here demonstrate that MVA, when used as a prime in a diversified vaccination, is clearly comparable with the regimen using the recombinant vaccinia in both the induction of cellular immune responses specific for the "self"-TAA transgene and in antitumor activity.     

Pyridoxal-5′-phosphate and pyridoxal biokinetics in aging Wistar rats

Biokinetic parameters of plasma pyridoxal-5′-phosphate (PLP) and pyridoxal (PL) disposition were studied in male Wistar rats aged 8 and 27 months kept from weaning on a purified diet containing 250 g casein and 6 mg pyridoxine·HCl per kg. Baseline plasma PLP concentration was lower in the older animals (514 ± 56 nmol/L for young and 317 ± 124 nmol/L for old animals), whereas baseline plasma PL concentration did not differ between age group (average 235 nmol/L for both young and old animals). We hypothesized lower baseline plasma PLP in the older animals was caused by an increased PLP elimination rate, a decreased PLP synthesis rate, or a combination of these processes. Observations from earlier in vitro experiments suggest age-related changes occur in vitamin B-6 metabolizing enzyme activities. In the in vivo experiments described here no age-related difference in plasma PLP elimination rate nor in plasma PLP synthesis rate was observed to explain the observed decrease in plasma PLP concentration with age.     

Psychological treatment of patients with psychogenic non-epileptic seizures: An outcome study.

INTRODUCTION: It is estimated that up to 25% of patients referred to specialised epilepsy centers suffer from psychogenic non-epileptic seizures (PNES). The prognosis is unfavourable and there are no generally accepted treatment protocols. METHOD: In this study, the effect of an uncontrolled, prospective inpatient treatment program for PNES patients is evaluated. The treatment is multidisciplinary and based on cognitive behavioural principles. Seizure control, general psychopathology, anxiety, depression, coping, dissociation and health related quality of life are evaluated. Twenty-two patients participated in the study of which 16 patients were followed 6 months after treatment. RESULTS: After follow-up, 81% of patients had a seizure reduction of over 50%, and half of them became seizure-free. Measures of anxiety, depression and dissociation tended to normalize, coping was more adequate and health related quality of life was increased slightly. In the period between the end of treatment and follow-up the most positive effects are maintained and even strengthened. Patients who became seizure-free at follow-up improved more on the psychological outcome measures than patients with continuing seizures. CONCLUSION: The outcome suggests effectiveness of the treatment. PNES patients may profit from a comprehensive, multidisciplinary treatment program following cognitive behavioural principles. Seizure cessation appears to be an important factor in the improvement of psychological functioning.     

Plasma free metanephrine measurement using automated online solid-phase extraction HPLC tandem mass spectrometry

BACKGROUND: Quantification of plasma free metanephrine (MN) and normetanephrine (NMN) is considered to be the most accurate test for the clinical chemical diagnosis of pheochromocytoma and follow-up of pheochromocytoma patients. Current methods involve laborious, time-consuming, offline sample preparation, coupled with relatively nonspecific detection. Our aim was to develop a rapid, sensitive, and highly selective automated method for plasma free MNs in the nanomole per liter range. METHODS: We used online solid-phase extraction coupled with HPLC-tandem mass spectrometric detection (XLC-MS/MS). Fifty microliters plasma equivalent was prepurified by automated online solid-phase extraction, using weak cation exchange cartridges. Chromatographic separation of the analytes and deuterated analogs was achieved by hydrophilic interaction chromatography. Mass spectrometric detection was performed in the multiple reaction monitoring mode using a quadrupole tandem mass spectrometer in positive electrospray ionization mode. RESULTS: Total run-time including sample cleanup was 8 min. Intra- and interassay analytical variation (CV) varied from 2.0% to 4.7% and 1.6% to 13.5%, respectively, whereas biological intra- and interday variation ranged from 9.4% to 45.0% and 8.4% to 23.2%. Linearity in the 0 to 20 nmol/L calibration range was excellent (R(2) > 0.99). For all compounds, recoveries ranged from 74.5% to 99.6%, and detection limits were <0.10 nmol/L. Reference intervals for 120 healthy adults were 0.07 to 0.33 nmol/L (MN), 0.23 to 1.07 nmol/L (NMN), and <0.17 nmol/L (3-methoxytyramine). CONCLUSIONS: This automated high-throughput XLC-MS/MS method for the measurement of plasma free MNs is precise and linear, with short analysis time and low variable costs. The method is attractive for routine diagnosis of pheochromocytoma because of its high analytical sensitivity, the analytical power of MS/MS, and the high diagnostic accuracy of free MNs.     

The postviral fatigue syndrome — an analysis of the findings in 50 cases

The clinical, pathological, electrophysiological, immunological and virological abnormalities in 50 patients with the postviral fatigue syndrome are recorded. These findings confirm the organic nature of the disease. A metabolic disorder, caused by persistent virus infection and associated with defective immunoregulation, is suggested as the pathogenetic mechanism.