Inhibition of fatty acid oxidation and in normal and hypoxic perfused rat hearts by 2-tetradecylglycidic acid.

Studies with a new fatty acid oxidation inhibitor, 2-tetradecylglycidic acid, showed that half-maximal inhibition of oleate oxidation occurred at concentrations of 3 × 10⁻⁶m. 2-Tetradecylglycidic acid also inhibited endogenous fatty acid oxidation, but had little effect on octanoate oxidation. The inhibition of long chain fatty acid oxidation produced by 2-tetradecylglycidic acid depended on its time exposure to the hearts. At low work loads it had no effect on left ventricular pressure development or aortic output, but was inhibitory at high work loads when the capacity for glucose oxidation was exceeded.The relationship of oleate concentration (with 2% albumin present) to pyridine nucleotide fluorescence and to the stimulation of oxygen consumption was examined using hearts perfused with glucose. Pyridine nucleotide fluorescence and oxygen consumption were both increased, with half-maximal effects occurring at 0.08 mm and 0.2 mm oleate, respectively. Oleate addition, both in the absence and presence of insulin, increased oxygen consumption to a greater degree than expected from the theoretical decrease of the $\text{P}\text{O}$ ratio associated with fatty acid oxidation. At fatty acid/albumin molar ratios of 2.5 or greater, contractility was impaired and oxygen consumption increased even further. Pyridine nucleotides remained reduced indicating the absence of an uncoupling effect on oxidative phosphorylation. The oxygen wasting effect of fatty acids is interpreted as caused by long chain fatty acyl-CoA formation and hydrolysis.In working heart preparations made hypoxic by lowering the perfusate oxygen content to about 35%, addition of 1 mm oleate to the perfusate resulted in a reversible decrease in left ventricular pressure development and aortic output. Perfusion with 5 × 10⁻⁵m 2-tetradecylglycidic acid for 40 min before oleate addition prevented this deleterious effect of oleate during hypoxia. Photographs of the surface pyridine nucleotide fluorescence showed that addition of oleate to the hypoxic heart resulted in an increase in the size and number of anoxic areas. Subsequent addition of 10⁻⁵m 2-tetradecylglycidic acid caused the anoxic areas to disappear. These results indicate that the deleterious effects of fatty acids on the hypoxic myocardium are due to an increased oxygen demand resulting from accelerated fatty acid oxidation.     

A non-invasive oral rinse assay predicts bone marrow engraftment and 6 months prognosis following allogeneic hematopoietic stem cell transplantation

J Oral Pathol Med (2012) 41 : 165–170 Background: We have previously shown in a pediatric Hematopoietic stem cell transplant (HSCT) population that a non‐invasive oral rinse can be used to monitor engraftment, neutrophil tissue delivery and susceptibility to infection post‐HSCT. Methods: Using the same oral rinse protocol, we studied neutrophil tissue delivery kinetics and its relationship to clinical parameters and outcomes following HSCT in 29 adult patients. Oral neutrophil counts were compared to circulating neutrophil levels, oral mucositis scores and patient health status at 6 months post‐HSCT. Results: Neutrophils were detected on average 8.4 ± 3.4 SD days earlier in the oral tissues than in the blood circulation, enabling us to confirm successful engraftment more than one week earlier than when using blood neutrophil counts alone. As well, in this population the time‐span between oral engraftment (OE) and blood engraftment (BE) was a consistent predictor of treatment outcome at 6 months following HSCT where a BE–OE of <6 days resulted in 100% of patients having a negative outcome. Conclusion: We conclude that monitoring the timing of neutrophil delivery to the oral tissues with a non‐invasive oral rinse has the potential to allow the physician to identify those patients who are at a high risk of HSCT failure within just a few weeks of the initiation of treatment.     

The addition of pyloroplasty as a new surgical approach to enhance effectiveness of gastric electrical stimulation therapy in patients with gastroparesis

Background Improvement of gastroparesis (GP) symptoms has been documented in patients treated with gastric electrical stimulation (GES), but acceleration of gastric emptying (GET) is unpredictable. The aim of our study was to evaluate the advantage of adding surgical pyloroplasty (PP) to GES for improvement of GET and control of symptoms in diabetes mellitus (DM), idiopathic (ID), and postvagotomy (P‐V) GP. Methods A total of 49 (17 – DM, 9 – ID, 23 – P‐V) consecutive GP patients: 38 female; mean age 42 (21–73 years); mean weight 158 lbs (102–245), underwent GES implantation, and 26 (53%) additionally received PP. Total Symptoms Score, 4‐h GET, adverse events (AEs), and days of hospitalizations were captured at baseline and at the last visit. Key Results The mean follow‐up was 7 months. Total Symptoms Score in patients who received Enterra and PP or GES alone significantly improved compared to their baseline scores (P < 0.001). GET improved by 64% at 4 h (P < 0.001) in patients with Enterra and PP, compared to 7% observed after GES therapy alone (ns). The most impressive acceleration of GET was seen in the P‐V group, who received both therapies (P = 0.004) and 8 (60%) of them normalized GET. No AEs accompanied the addition of PP to the Enterra surgery. Conclusions & Inferences (i) In drug‐refractory GP the addition of PP to GES substantially accelerated GET; (ii) The GET response in P‐V group was the most impressive; (iii) Significant symptom reductions were achieved by both procedures; and (iv) PP added to GES may sustain better long‐term symptoms control particularly in the P‐V setting.     

Values as Moderators of the Association between Interpersonal-Psychological Constructs and Suicidal Ideation among Veterans

This study examined whether valuing relationships, achievement, and security moderated the association between interpersonal-psychological constructs (Joiner, 2005 Joiner, T. E. Jr. (2005). Why people die by suicide. Cambridge, MA: Harvard University Press.[Crossref] , [Google Scholar]) and suicidal ideation (SI). A total of 122 veterans completed the Interpersonal Needs Questionnaire, Survey of Life Principles, and Beck Scale for Suicide Ideation. Valuing relationships moderated the association between thwarted belongingness and SI. Specifically, thwarted belongingness predicted SI among veterans who reported moderate and high, but not low, levels of valuing relationships. The estimated impact of perceived burdensomeness on SI was stronger at higher levels of valuing relationships, but only approached statistical significance. Valuing achievement and security did not moderate the association between perceived burdensomeness and SI. Future research should continue to examine specific values as they relate to interpersonal-psychological constructs and suicidal behavior.