Journal of investigative medicine : the official publication of the American Federation for Clinical Research
-
Primary (degenerative) mitral valve (MV) disease is a result of structural remodeling due to degenerative and adaptive changes of MV tissue. We hypothesized that in patients with primary MV disease undergoing surgery for severe mitral regurgitation (MR), a distinct genetic expression profile within the MV leaflet tissue could be identified as compared with patients without MV disease. Tissue samples from the MV leaflets of 65 patients undergoing MV surgery for MR due to primary MV disease and 4 control cadavers without MV disease were collected and analyzed. ⋯ These five networks have been previously implicated in pathophysiological cardiac abnormalities, including inhibited contractility of the heart and fatty acid oxidation as well as activation of apoptosis of smooth muscle cells, cardiac degeneration, and hypertrophy of cardiac cells. MV tissue in patients with primary MV disease demonstrated distinct genetic expression patterns as compared with normal controls. Further studies are necessary to determine whether the molecular pathways identified in this experiment may represent potential therapeutic targets to prevent degeneration of MV tissue leading to severe MR.
-
The biological activity and effects of circulating sphingosine 1-phosphate (S1P) might be dependent on the carrier protein. Although S1P is known to be a biomarker for osteoporotic fracture (OF), its role according to its carrier protein (high-density lipoprotein (HDL), low-density lipoprotein (LDL), or albumin) has not yet been studied. We measured the protein-bound S1P levels and bone mineral density (BMD) in 58 postmenopausal women with OF and 58 age-matched and body mass index-matched postmenopausal women without OF. ⋯ Before adjustment, the OR for OF was higher in subjects in the highest quartile for total S1P (OR 5.36, 95% CI 1.22 to 23.63) or albumin-bound S1P (OR 4.48, 95% CI 1.22 to 16.42). After adjustment for confounders including BMD, statistical significance persisted only for total S1P (OR 2.23, 95% CI 1.12 to 4.81). These findings suggest that the positive association of S1P with OF is mainly due to level of total plasma S1P and not due to the differing contributions from specific carrier protein-bound fractions.
-
Increased aortic stiffness may contribute to kidney damage by transferring excessive flow pulsatility to susceptible renal microvasculature, leading to constriction or vessel loss. We previously demonstrated that 5 weeks of dietary sodium restriction (DSR) reduces large-elastic artery stiffness as well as blood pressure in healthy middle-aged/older adults with moderately elevated systolic blood pressure (SBP) who are free from chronic kidney disease (CKD). We hypothesized that DSR in this cohort would also reduce urinary concentrations of renal tubular injury biomarkers, which predict incident CKD in the general population. ⋯ Results were similar when normalized to urinary creatinine (urinary creatinine did not change between conditions). Concentrations of another kidney tubular injury biomarker, kidney injury molecule-1, were below the detectable limit in all but one sample. In conclusion, DSR reduces an established clinical biomarker of kidney tubular damage in adults with moderately elevated SBP who are free from prevalent kidney disease.
-
Normothermia (36.5°C-37. 5°C) at the time of admission to the neonatal intensive care unit (NICU) in extremely low birthweight (ELBW) infants (birth weight <1000 g) is associated with decreased morbidity and mortality, decreased length of stay and hospital costs. We designed a thermoregulation bundle to decrease hypothermia (<36.5°C) in ELBW infants with a multidisciplinary perinatal quality improvement initiative that included the following key interventions: dedicated delivery room (DR)/operating room (OR) for all preterm deliveries of ≤32 weeks with DR/OR temperature set 24/7 at 74°F by the hospital engineering staff, use of exothermic mattress, preheated radiant warmer set at 100% for heat prior to delivery, servo-controlled mode after the neonate is placed on the warmer, and use of plastic wrap, head cap and warm towels. A total of 200 ELBW infants were admitted to our NICU between January 1, 2014 and December 31, 2019. ⋯ No case of moderate hypothermia (32°C-36°C) was seen in our infants. Our target rate of less than 10% hypothermia was reached in ELBW infants over the last 2 years with no cases of moderate hypothermia in 6 years. Eliminating hypothermia among ELBW remains a challenge and requires team effort and continuous quality improvement efforts.
-
Patients with acute respiratory failure often have hyperglycemia. Elevated glucose levels could cause acute lung injury through the production of advanced glycation end products. We measured glucose, advanced glycation end products, glycated albumin, circulating glycated hemoglobin, and soluble receptor for advanced glycation end product (sRAGE) levels on admission, at 24 hours, and at 72 hours in 40 patients with acute respiratory failure requiring mechanical ventilation. ⋯ Overall sRAGE levels were similar to controls, but patients with dense infiltrates on chest X-ray had increased levels compared with patients who did not have these dense infiltrates on the day of admission. Patients with acute respiratory failure requiring mechanical ventilation have decreased levels of advanced glycation end products and increased levels of circulating glycated hemoglobin. The results from this pilot study suggest that the acute stress associated with respiratory failure might create glycated proteins which could contribute to disease pathogenesis.