Hemin is released from hemoglobin after CNS hemorrhage and is present at high micromolar concentrations in intracranial hematomas. This highly reactive compound is potentially cytotoxic via a variety of oxidative and nonoxidative mechanisms. However, despite its clinical relevance, little is known of its effect on neuronal cells. In this study, we tested the hypotheses that hemin is toxic to human neurons at physiologically relevant concentrations and that its toxicity is iron dependent and oxidative. A homogeneous population of neuron-like cells was produced by sequential treatment of SH-SY5Y cells with retinoic acid and brain-derived neurotrophic factor, using the protocol of Encinas et al. Hemin exposure for 24 hr resulted in cell death that progressively increased between 3 and 30 microM (EC(50) approximately 10 microM); protoporphyrin IX, the iron-free congener of hemin, was not toxic. Cell death commenced at 14 hr and was preceded by a marked increase in cellular reactive oxygen species (ROS). Most injury and ROS production were prevented by concomitant treatment with an equimolar concentration of the lipid-soluble iron chelator phenanthroline; the water-soluble chelator deferoxamine was also effective at concentrations of 0.1 mM or higher. Heme oxygenase-2 was constitutively expressed by these cells, and heme oxygenase-1 was induced by hemin. Heme oxygenase inhibition attenuated ROS generation and reduced injury by about one-third. Cell death was also prevented with the sulfhydryl reducing agents glutathione and mercaptoethanol. Nuclear morphology in the hours prior to cell lysis revealed a predominantly homogenous staining pattern; the percentage of fragmented nuclei was increased only at 4 hr and then accounted for only 1.45% +/- 0.25% of cells. The general caspase inhibitor zVAD-fmk had no effect on cell viability. These results suggest that hemin is toxic to human neuron-like cells at concentrations that are less than 3% of those observed in intracranial hematomas. In this model, its toxicity is iron dependent, oxidative, and predominantly necrotic.

Rationale Blood gas analysis is often used to assess acid–base, ventilation, and oxygenation status in critically ill patients. Although arterial blood gas (ABG) analysis remains the gold standard, venous blood gas (VBG) analysis has been shown to correlate with ABG analysis and has been proposed as a safer less invasive alternative to ABG analysis. Objective The purpose of this study was to evaluate the correlation of VBG analysis plus pulse oximetry (SpO2) with ABG analysis. Methods We performed a prospective cohort study of patients in the emergency department (ED) and intensive care unit (ICU) at a single academic tertiary referral center. Patients were eligible for enrollment if the treating physician ordered an ABG. Statistical analysis of VBG, SpO2, and ABG data was done using paired t test, Pearson χ2, and Pearson correlation. Main Results There were 156 patients enrolled, and 129 patients completed the study. Of the patients completing the study, 53 (41.1%) were in the ED, 41 (31.8%) were in the medical ICU, and 35 (27.1%) were in the surgical ICU. The mean difference for pH between VBG and ABG was 0.03 (95% confidence interval: 0.03–0.04) with a Pearson correlation of 0.94. The mean difference for pCO2 between VBG and ABG was 4.8 mm Hg (95% confidence interval: 3.7–6.0 mm Hg) with a Pearson correlation of 0.93. The SpO2 correlated well with PaO2 (the partial pressure of oxygen in arterial blood) as predicted by the standard oxygen–hemoglobin dissociation curve. Conclusion In this population of undifferentiated critically ill patients, pH and pCO2 on VBG analysis correlated with pH and pCO2 on ABG analysis. The SpO2 correlated well with pO2 on ABG analysis. The combination of VBG analysis plus SpO2 provided accurate information on acid–base, ventilation, and oxygenation status for undifferentiated critically ill patients in the ED and ICU.

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Diseases that cause vomiting, diarrhea, constipation, and gastroenteritis are major problems for populations worldwide. Patients, particularly infants, elderly, and immunocompromised individuals, may present at any point in a wide spectrum of disease states, underscoring the need for the clinician to treat these ailments aggressively. Several promising new treatment modalities, from oral rehydration solutions to antiemetic therapies, have been introduced over the past decade. Future directions include the use of probiotic agents and better tolerated rehydration solutions. Gastrointestinal disease will continue to be a focus worldwide in the search for better ways to cure illnesses associated with vomiting and diarrhea.

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