Intranasal Erythropoietin Protects CA1 Hippocampal Cells, Modulated by Specific Time Pattern Molecular Changes After Ischemic Damage in Rats.

Erythropoietin, a multitarget molecule exhibited neuroprotective properties, especially against cerebral ischemia. However, little effort has been made to determinate both the administration pathway and doses that diminishes neuronal damage. In this study, we investigate the effect on CA1 region of different intranasal doses of rHuEPO (500, 1000 and 2500 IU/kg) applied in distinct post-damage times (1, 6, and 24 h) against ischemic cellular damage. Furthermore, most effective dose and time were used to evaluate gen and protein expression changes in 3 key molecules (EPO, EPOR, and ßcR). We established that CA1-region present histopathological damage in this ischemia model and that rHuEPO protects cells against damage, particularly at 1000 IU dose. Molecular data shows that EPO and EPOR gene expression are upregulated in a short term after damage treatment with rHuEPO (1 h); oppositely, BcR is upregulated in ischemic and Isc + EPO. Protein expression data displays no changes on EPO expression in evaluated times after treatment, but a tendency to increase 24 h after damage; in the opposite way, EPOR is upregulated significantly 6 h after treatment and this effect last until 24 h. So, our data suggest that a single intranasal dose of rHuEPO (1 h post-injury) provides histological neurorestoration in CA1 hippocampal region, even if we did not observe a dose-dependent dose effect, the medium dose evaluated (1000 UI/kg of b.w.) was more effective and sufficient for induces molecular changes that provides a platform for neuroprotection.

Severe acute metabolic acidosis (acute beriberi): an avoidable complication of total parenteral nutrition.

Total parenteral nutrition is one of the most important recent advances in medicine. The delivery of total parenteral nutrition, however, can be associated with a broad spectrum of complications ranging from mechanical (catheter related) to metabolic. We have recently seen a previously unreported complication of total parenteral nutrition - three patients maintained on total parenteral nutrition, who did not receive vitamins and experienced the acute onset of life-threatening metabolic acidosis with pH values as low as 6.70. All responded promptly and completely to the administration of intravenous thiamine, and thus were probably examples of acute beriberi. Acute beriberi is a well-documented syndrome which usually occurs in nutritionally compromised individuals outside the hospital setting who lack thiamine in their diet. Without thiamine, glucose cannot enter the Krebs cycle in order to be completely oxidized for energy production and therefore, accumulates as lactic acid. This lactic acidosis is refractory to any treatment except thiamine and will result in cardiovascular collapse if the vitamin is not administered.