Mice have a transcribed L-threonine aldolase/GLY1 gene, but the human GLY1 gene is a non-processed pseudogene

BACKGROUND: There are three pathways of L-threonine catabolism. The enzyme L-threonine aldolase (TA) has been shown to catalyse the conversion of L-threonine to yield glycine and acetaldehyde in bacteria, fungi and plants. Low levels of TA enzymatic activity have been found in vertebrates. It has been suggested that any detectable activity is due to serine hydroxymethyltransferase and that mammals lack a genuine threonine aldolase. RESULTS: The 7-exon murine L-threonine aldolase gene (GLY1) is located on chromosome 11, spanning 5.6 kb. The cDNA encodes a 400-residue protein. The protein has 81% similarity with the bacterium Thermotoga maritima TA. Almost all known functional residues are conserved between the two proteins including Lys242 that forms a Schiff-base with the cofactor, pyridoxal-5'-phosphate. The human TA gene is located at 17q25. It contains two single nucleotide deletions, in exons 4 and 7, which cause frame-shifts and a premature in-frame stop codon towards the carboxy-terminal. Expression of human TA mRNA was undetectable by RT-PCR. In mice, TA mRNA was found at low levels in a range of adult tissues, being highest in prostate, heart and liver. In contrast, serine/threonine dehydratase, another enzyme that catabolises L-threonine, is expressed very highly only in the liver. Serine dehydratase-like 1, also was most abundant in the liver. In whole mouse embryos TA mRNA expression was low prior to E-15 increasing more than four-fold by E-17. CONCLUSION: Mice, the western-clawed frog and the zebrafish have transcribed threonine aldolase/GLY1 genes, but the human homolog is a non-transcribed pseudogene. Serine dehydratase-like 1 is a putative L-threonine catabolising enzyme

IMPROVING NEUROLOGIC OUTCOME IN CARDIAC SURGERY PATIENTS WITH A GOAL-ORIENTED THERAPY PROTOCOL BASED ON CEREBRAL REGIONAL OXYGEN SATURATION

IMPROVING NEUROLOGIC OUTCOME IN CARDIAC SURGERY PATIENTS WITH A GOAL-ORIENTED THERAPY PROTOCOL BASED ON CEREBRAL REGIONAL OXYGEN SATURATION F. Franchi, B. Biagioli, A. Tabucchi, S. Scolletta University of Siena, Siena, Italy INTRODUCTION. NIRS (near infrared spectroscopy) is a neuro-monitoring tool that provides cerebral regional oxygen saturation (rSO2). OBJECTIVES. We hypothesized that a goal-directed therapy (GDT) protocol based on rSO2 values would be associated with reduced incidence of postoperative neurologic complications (PNC) in high-risk cardiac surgery (CS) patients. METHODS. 85 high-risk CS patients (mean age 71 ± 9) were monitored during CS with NIRS (cNIRS group). Intraoperative interventions were based on a GDT protocol aimed at improving cerebral rSO2 and blood flow (i.e., increasing arterial oxygen content with red blood cell transfusions and FiO2; increasing systemic blood flow and cerebral perfusion pressure with fluids, inotropic, and vasoactive drugs and increasing pump-flow during cardiopulmonary bypass). cNIRS group was compared with 100 patients (mean age 73 ± 6) (not monitored with cerebral NIRS, N-cNIRS group) who were selected from a historical database using a propensity-matching analysis. Neuron-specific enolase (NSE) and S-100B protein were collected at different times in the cNIRS group. RESULTS. PNC resulted 21 % in the cNIRS group and 35 % in N-cNIRS group (p\0.05). N-cNIRS group showed longer times of mechanical ventilation (MV) (150.3 ± 274.9 vs 29.9 ± 65 h, p = 0.02) and ICU stay (13.3 ± 14.7 vs 3.4 ± 3.9 days, p = 0.01) than cNIRS group. In the cNIRS group, preoperative rSO2 values were signifi- cantly lower in the patients who exhibited PNC than those who had good neurologic outcome (59.6 ± 7.6 vs 63.4 ± 7.8 %, p = 0.04). An inverse correlation was found between the lowest values of intraoperative cerebral rSO2 and the length of MV (r = -0.31, p = 0.04) and ICU stay (r = -0.43, p = 0.003). Only the peak of NSE, measured 6 h after CS, showed significant difference between patients who developed PNC and those who did not (p = 0.02). CONCLUSIONS. In our cohort of CS patients, NSE and S-100B protein were poor pre- dictors of PNC. Conversely, the lower the preoperative cerebral rSO2, the poorer the neurologic outcome. A GDT protocol based on NIRS values, aimed at improving cerebral rSO2 and blood flow, might reduce PNC in high-risk CS patients. REFERENCE(S). Murkin JM, Adams SJ, Novick RJ, et al. Monitoring brain oxygen saturation during coronary bypass surgery: a randomized, prospective study. Anesth Analg. 2007;104(1):51-8

Relationships between hemodynamic parameters and myocardial energy and antioxidant status in heart transplantation.

PMID: 1281847

Preservation of myocardial energy status by bovine hemoglobin solutions during ischemia.

Compared to murine and human hemoglobin, bovine hemoglobin has a less exothermic oxygen binding and delivers oxygen even at low temperatures. This property could improve oxygen availability for myocytes during hypothermic arrest of hearts. The aim of this study was to evaluate the advantage of using cardioplegic solutions enriched with bovine hemoglobin when storing rat hearts. Hearts excised from rats after perfusion with different cardioplegic solutions (Celsior, Celsior plus 4% human hemoglobin, Celsior plus 4% and 8% bovine hemoglobin) were compared. Biopsies were obtained from the beating hearts before cardioplegic infusion and during a 48 h period of cold storage. Adenosine triphosphate, its catabolites and markers of oxidative stress were measured as indices of preservation. The results show that bovine hemoglobin-enriched solutions highly improve adenosine triphosphate content, decreasing its catabolites; no significant changes in antioxidant status were evident. The statistically significant difference was evident up to 6 h of storage. Doubling the concentration of bovine hemoglobin produces only slight improvement. Alternative hemoglobins with different properties may improve and prolong heart storage. As bovine hemoglobin delivers oxygen even at low temperatures, it improves energy content and anabolic reactions, without decreasing oxidative stress

Relationship between hemodynamic parameters and myocardial energy and antioxidant status in heart transplantation.

PMID: 1281847

Oxidative stress: clinical implications in cardiac surgery.

PMID: 1100302

Role of bovine hemoglobin enriched cardioplegia in myocardial preservation

[No abstract available