Neurotherapeutic potential of erythropoietin after ischemic injury of the central nervous system

Erythropoietin(EPO) is one of the most successful biopharmaceuticals in history and is used for treating anemia of different origins. However, it became clear that EPO could also work in a neuroprotective, antiapoptotic, antioxidative, angiogenetic and neurotropic way. It causes stimulation of cells to delay cell apoptosis, especially in the central nervous system. In rodent models of focal cerebral ischemia, EPO showed an impressive reduction of infarct size by 30% and improvement of neurobehavioral outcome by nearly 40%. A large animal model dealing with ischemia and reperfusion of the spinal cord showed that EPO could reduce the risk of spinal cord injury significantly. In addition, some clinical studies tested whether EPO works in real live clinical settings. One of the most promising studies showed the innocuousness and improvements in follow-up, outcome scales and in infarct size, of EPO-use in humans suffering from ischemic stroke. Another study ended unfortunately in a negative outcome and an increased overall death rate in the EPO group. The most possible reason was the involvement of patients undergoing simultaneously systemic thrombolysis with recombinant tissue plasminogen activator. An experimental study on rats demonstrated that administration of EPO might exacerbate tissue plasminogen activator-induced brain hemorrhage without reducing the ischemic brain damage. This case shows clearly how useful animal models can be to check negative side effects of a treatment before going into clinical trials. Other groups looked in human trials at the effects of EPO on the outcome after ischemic stroke, relation to circulating endothelial progenitor cells, aneurysmal subarachnoid hemorrhage, traumatic brain injury, hemoglobin transfusion thresholds and elective first-time coronary artery bypass surgery. Most of the results were positive, but are based mostly on small group sizes. However, some of the most neglected facts when focusing on experimental setups of ischemia of the central nervous system are issues like age and comorbidities. It might be extremely worthy to consider these points for future projects, because EPO might influence all these factors.     

Role of retinol in protecting epithelial cell damage induced by Clostridium difficile toxin A

Vitamin A (retinol), a fat-soluble vitamin, is an essential nutrient for the normal functioning of the visual system, epithelial cell integrity and growth, immunity, and reproduction. Our group has investigated the effect of high doses of oral vitamin A on early childhood diarrhea in our prospective community-based studies from Northeast Brazil and found a beneficial role in reducing the mean duration but not incidence of diarrheal episodes. In this study, we explored the role of retinol supplementation in intestinal cell lines following Clostridium difficile toxin A (TxA) challenge. C. difficile is the most common anaerobic pathogen borne with antibiotic-borne diarrhea and pseudomembranous colitis. Since retinol is critical for the integrity of tight junctions and to modulate the cell cycle, we have focused on changes in transepithelial electrical resistance (TEER) in Caco-2, a more differentiated intestinal cell line, and on models of cell proliferation, migration and viability in IEC-6 cells, an undifferentiated crypt cell line, following TxA injury. In this model, retinol therapy reduced apoptosis, improved cell migration and proliferation, and prevented the reduction in TEER, following C. difficile TxA challenge in a glutamine-free medium. These results suggest the role of retinol in protecting intestinal epithelial barrier function from C. difficile TxA enterotoxic damage.     

THE NATIONAL BIRTH CENTER STUDY Part II—Intrapartum and Immediate Postpartum and Neonatal Care

Part II of a three-part report of the National Birth Center Study describes care provided to 11,814 women and their newborns during and after labor and delivery until they were transferred or discharged from the birth centers. There were few low birth weight or preterm or postterm births, but more macrosomic babies than among all U.S. births during the same time period. Certified nurse-midwives provided most of the intrapartum care, which is described in the context of medically recommended standards and data that describe care provided to low-risk women giving birth in U.S. hospitals. Birth center care deviated from typical hospital care in several ways. Birth center clients were much less likely to receive central nervous system depressants, anesthesia, continuous electronic fetal monitoring, induction and/or augmentation of labor, intravenous infusions, amniotomies, or episiotomies, and they had relatively few vaginal examinations. They were more likely to eat solid food during labor and to take showers and/or baths Nulliparity was strongly associated with longer first stage labors and longer labor was associated with more frequent use of many kinds of interventions. Infant birth weight, mother's position during delivery, and forceps- or vacuum-assisted deliveries are examined in relation to episiotomies and lacerations and tears.     

Hydroxamate siderophore production by opportunistic and systemic fungal pathogens.

It has been suggested that siderophores may function as virulence factors. There have been few studies on production of siderophores by opportunistic and pathogenic fungi. We examined siderophore production by Absidia corymbifera, Aspergillus niger, Rhizopus arrhizus, Rhizopus oryzae, Blastomyces dermatitidis, Histoplasma capsulatum, Sporothrix schenickii, Candida albicans, and Trichophyton mentagrophytes. Fungi were cultured at 37 and 27 degrees C in a chemically defined low-iron media (0.2 microM Fe). Culture supernatants were assayed for siderophores by two nonspecific methods [FeCl3 and Fe(ClO4)3] and three chemically specific assays (catechol, 2,3-dihydroxybenzoate, and hydroxamate). All fungi secreted siderophores. Only siderophores of the hydroxamate type were found. More siderophore was produced at 27 degrees C than at 37 degrees C. The present study adds eight fungi to the list of known siderophore producers and confirms siderophore production by H. capsulatum.     

Failure to recover after anesthesia attributed to a transient dissociative state

Failure of a patient to recover rapidly after anaesthesia is a rare event, due to various causes, including medication related effects, metabolic disturbances or neurologic insults. We report a case in a middle aged physically healthy woman who failed to recover promptly after intravenous anaesthesia. Propofol was administered for 20 minutes. Results of neurologic assessment were normal, as were laboratory tests and CT-scan. Four hours after completion of the anaesthesia, return to consciousness occurred spontaneously. The patient had a history of depressive symptoms. However the psychiatric assessment was unremarkable. We hypothesise that she developed a transient dissociative disorder.