Glutathione peroxidase inhibits cell death and glial activation following experimental stroke

Stroke is a leading cause of morbidity and mortality in major industrial countries. Many factors contribute to the cellular damage resulting from ischemia-reperfusion (I-R). Growing evidence indicates that reactive oxygen species (ROS) contribute significantly to this process, though their exact mechanism of action is mostly unknown. We have examined the mechanism of protection against I-R injury in transgenic mice that overexpress human glutathione peroxidase (hGPx1), using a focal cerebral I-R model. In this model, transgenic animals show significant reduction of necrotic as well as apoptotic cell death in vulnerable brain regions as demonstrated by TUNEL staining, DNA laddering and ELISA assays. We also observed decreased astrocytic and microglial activation in ischemic brains of animals overexpressing hGPx1. In wild-type mice, neuronal cell death was accompanied with compromise of vascular integrity, edema and neutrophil infiltration, whereas GPx1 mice revealed significant preservation of tissue structure and decreased infiltration of acute inflammatory cells. These results indicate that glutathione peroxidase-sensitive ROS play an important role in regulation of cell death during cerebral I-R as well as in brain inflammatory reactions.     

Telemedicine and spaceflight

Medical assessment and treatment of crews during spaceflight is primarily perfomed by the Earth-based medical staff analyzing information received by telemetry and onboard preventive and medical treatment facilities. In the coming decades, the building of the International Space Station (ISS) will be the most important near-Earth space exploration project. Remote monitoring and distance support of the crewmembers by the Earth-based clinical medicine specialists will become increasely important. The international nature of the ISS will require integrating medical support systems of the participating countries. Consideration must also be given to biomedical ethics and the confidentiality of the medical information exchanged. In Russia, the construction of the telemedicine network for the Russian node of the ISS has been completed. It is evident that during interplanetary flight biomedical problems will be much more difficult than during orbital flights of the same duration. Such a long-duration flight will require development of a special telemedical support system, as well as onboard facilities, which will present many new challenges. This new system will involve the integration of information technologies with biology, as well as physics and chemistry, representing a new interdisciplinary technological breakthrough.     

A new live animal training model for off-pump coronary bypass surgery

Training models are needed to perform accurate off-pump coronary artery bypass (OPCAB) surgery and to test evolving new technologies like minimally invasive devices and robotics. We describe a simple, effective and reproducible live animal training model to perform multiple arterial anastomoses on the beating heart that would maximize the use of available resources for training purposes.     

Long-term theophylline treatment changes the effects of angiotensin II and adenosinergic agents on the seizure threshold

The effects of angiotensin II (ANG II), sarmesin, losartan, PD 123319, and adenosine A (1) receptor agonist N(6)-cyclopentyladenosine (CPA) administered i.c.v. in untreated and in theophylline-treated male mice (50 mg/kg i.p. twice daily for 14 days) were studied on the pentylenetetrazol (PTZ) seizure threshold. The threshold was increased after long-term theophylline treatment. ANG II, sarmesin, and CPA increased the threshold in theophylline-untreated mice, whereas it decreased the threshold in theophylline-treated animals. Losartan did not change the threshold in theophylline-untreated mice but decreased it in theophylline-treated animals. PD 123319 did not change the seizure threshold both in theophylline-untreated and -treated mice. Taken together, the data demonstrated that repeated exposure to theophylline selectively changes the effects of ANG II and adenosinergic agents on the PTZ seizure threshold. The results indicate that both angiotensin AT(1) and adenosine A(1) receptor subtypes could possess interactive mechanisms of adaptation to chronic theophylline treatment.     

Does Inflammation in an Autoimmune Disease Differ from Inflammation in Neurodegenerative Diseases? Possible Implications for Therapy

Accumulating evidence suggests that neurodegenerative diseases of the central nervous system (CNS) are associated with a local inflammatory response. CNS autoimmune diseases are also associated with inflammation. Does this mean that all neurodegenerative diseases are autoimmune in nature? Does it imply that autoimmune and neurodegenerative diseases are both eligible for the same therapy? What distinguishes between the two types of disease? Do they differ both in etiology and in pathology, or do they have different etiologies but similar pathology and progression? In this minireview we offer a new view of the inflammatory differences between neurodegenerative and autoimmune diseases in the CNS and discuss the implications for therapy.     

CHEK2-positive breast cancers in young Polish women.

PURPOSE: To investigate the contribution of CHEK2 mutations to early-onset breast cancer in Poland and to establish the characteristic features of these cancers. EXPERIMENTAL DESIGN: We studied 3,228 women diagnosed with breast cancer under the age of 51 years and 5,496 population controls. CHEK2 mutations were detected by RFLP-PCR or allele-specific oligonucleotide-PCR assays. Clinical and pathologic features of CHEK2-positive cases and CHEK2-negative cases were compared. RESULTS: A truncating CHEK2 mutation (1100delC or IVS2+1G>A) was seen in 47 of 3,228 cases and in 34 of 5,496 controls (odds ratio, 2.4; P = 0.0001). The CHEK2 I157T missense mutation was present in 207 of 3,228 cases, compared with 264 of 5,496 controls (odds ratio, 1.4; P = 0.002). Breast cancers in women with a CHEK2 mutation were more commonly of lobular histology (21.5% versus 15.8%; P = 0.05), of size >2 cm (54.8% versus 43.5%; P = 0.01), or of multicentric origin (28.7% versus 19.5%; P = 0.01) than were cancers from women without a CHEK2 mutation. Bilateral cancers were equally common in both subgroups. CONCLUSION: Three founder alleles in CHEK2 contribute to early-onset breast cancer in Poland. Breast tumors which arise in carriers of CHEK2 mutations seem to be similar to those of breast cancers in the population at large.     

Long-term follow-up after surgical treatment of cerebellar astrocytomas in 100 children

A retrospective study was performed in 100 children, who were operated on between 1954 and 1984 for cerebellar astrocytoma. Twenty-nine patients died during the 1st month after the operation. Of the patients who survived, 24 lived up to 5 years, 17 up to 10 years, and 30 lived 20 or more years. In 22 cases, tumor recurrence was the reason for reoperation. Radiation therapy was used in 25 cases with histological malignancy and/or after partial removal of the tumor. The analysis in 6 cases with brainstem involvement allowed us to conclude that in such cases the prognosis is poor with regard to survival. Although total removal of cerebral astrocytomas appears to be the most effective form of treatment, we are of the opinion that even subtotal excision may be compatible with long-term survival. This suggests that many of these tumors may show benign biological behavior.Presented at the XIth Meeting of the European Society for Pediatric Neurosurgery, Naples, 1988     

Possible morphological substrates for GABA-mediated presynaptic inhibition in the lamprey spinal cord

Gamma-aminobutyric acid (GABA) neurons intrinsic to the lamprey spinal cord are known to modulate synaptic transmission from interneurons active during locomotion and from mechanosensory dorsal cells. Many of these physiological effects are presynaptic. To establish the morphological substrates for these axo-axonic interactions, an ultrastructural analysis was performed with an antiserum to fixed GABA. The GABA immunoreactivity (ir) was detected by postembedding peroxidase-antiperoxidase and immunogold techniques. GABA-ir terminals were found to make appositions with unlabelled axons located in the dorsal columns and in the ventrolateral aspect of the spinal cord. In the ventrolateral part of the cord, similar appositions between different GABA-ir terminals were also observed. The immunolabelled terminals contained spherical to pleomorphic synaptic vesicles, and also glycogen granules and dense core vesicles. In some cases, the fine structure of the contacts between immunogold-labelled terminals and unlabelled axons suggested a synaptic relationship. Such a relation was found in a relatively small proportion (2–3%) of the appositions studied. These specializations were always observed in close relation to an output synapse of the postsynaptic axon. It is suggested that the axo-axonal contacts described may provide an effective modulation of the synaptic transmission from axons in the lamprey spinal cord. © 1993 Wiley-Liss, Inc.