Influence of hydroxyurea on fetal hemoglobin production in vitro

Cytotoxic drugs increase circulating fetal hemoglobin levels. We examined the mechanism by measuring the fetal hemoglobin produced per BFU-E-derived erythroblast following hydroxyurea treatment in vivo and in vitro. Treatment of four sickle cell patients increased the percentage of circulating F reticulocytes. The frequencies of bone marrow or peripheral blood BFU-E or CFU-E-derived colonies and their fetal hemoglobin content were unaffected. In all cases, the number of erythroid cells/progenitor-derived colony increased. To explore further the effect of hydroxyurea on fetal hemoglobin production, we added 50 mumol/L hydroxyurea to cultures of peripheral blood BFU-E-derived erythroblasts on 1 of 9 days (day 5 through 13) to nine samples. These BFU-E were derived from the peripheral blood of normal donors, sickle trait donors, and sickle cell anemia patients and from the bone marrows of monkeys. This concentration of hydroxyurea was selected so that the frequency of BFU-E and their size was moderately decreased. Addition of hydroxyurea to these progenitor-derived erythroid cells had no effect on fetal hemoglobin content per cell. Neither did transient exposure of progenitors to hydroxyurea prior to culture in nontoxic concentrations (0 to 500 mumol/L) result in a significant increase in fetal hemoglobin content in progenitor-derived erythroblasts. These data suggest that hydroxyurea does not directly alter the HbF program expressed by progenitor-derived erythroid cells. Instead, it enhances hemoglobin F content secondarily, possibly by inducing alterations in erythropoiesis.     

Soy isoflavones improve cardiovascular disease risk markers in women during the early menopause

Background

Hormone replacement therapy may be beneficial for cardiovascular disease risk (CVR) in post-menopausal women. Soy isoflavones may act as selective estrogen receptor modulators. The aim of this study was to evaluate whether soy isoflavones had an effect on CVR markers.

Proenkephalin products are stored in the sperm acrosome and may function in fertilization.

Previous studies have shown that spermatogenic cells are a major source of testicular RNA encoding the opioid peptide precursor proenkephalin, suggesting that proenkephalin-derived peptides may function as intratesticular paracrine factors produced by male germ cells. However, direct evidence for the production of proenkephalin by spermatogenic cells has been lacking. In this report, we have used polysome profile analysis, peptide quantitation, and immunocytochemistry to show that proenkephalin products are synthesized during spermatogenesis and are retained within spermatozoa of humans, hamsters, rats, and sheep. We further show that these peptides are stored in the sperm acrosome and are depleted from sperm following the acrosome reaction, an exocytotic event required for fertilization. Proenkephalin products thus may serve a dual function as sperm acrosomal factors released during the fertilization process as well as intratesticular regulators secreted by spermatogenic cells.     

Can ficolin‐2 (L‐ficolin) insufficiency be established by a single serum protein measurement?

Serum ficolin‐2 was measured in multiple (2‐27) samples from 68 paediatric sepsis patients. Fourteen individuals (21%) gave values that included a change in status from ‘normal’ to ‘insufficient’ or vice versa. Therefore, if possible, ficolin‐2 concentration should be determined in samples obtained when a disease is inactive.     

Short-term glucose variability in healthy volunteers is not associated with raised oxidative stress markers

It is unknown whether glycaemic variability adds to the risk of microvascular complications of diabetes over and above the mean glucose value for a patient. We examined the effect of purposefully induced short‐term glycaemic variability on oxidative stress markers. Eleven healthy subjects underwent three sequential glycaemic states; sustained hyperglycaemia, sustained euglycaemia and variable glycaemia, using glycaemic clamps for 3 h. Twenty‐four hours urinary 8‐isoprostane‐PGF2α was measured before and after each glycaemic state to assess oxidative stress. The median and interquartile range of the urinary 8‐iso‐PGF2α in ng/24 h were (1373, 513), (996, 298) and (1227, 472) for the euglycaemic, hyperglycaemic and variable states, respectively. There was no significant difference in urinary isoprostanes between the three different states; mean ranks 20.9, 11.9 and 18.2 for the euglycaemic state, hyperglycaemic state and glycaemic variability state, respectively, p = 0.083. In conclusion, we did not see a significant increase in the urinary isoprostanes when glycaemic variability was induced under controlled conditions in healthy individuals.     

National Estimates of Exposure to Traumatic Events and PTSD Prevalence Using DSM‐IV and DSM‐5 Criteria

Prevalence of posttraumatic stress disorder (PTSD) defined according to the American Psychiatric Association's Diagnostic and Statistical Manual fifth edition (DSM‐5; 2013) and fourth edition (DSM‐IV; 1994) was compared in a national sample of U.S. adults (N = 2,953) recruited from an online panel. Exposure to traumatic events, PTSD symptoms, and functional impairment were assessed online using a highly structured, self‐administered survey. Traumatic event exposure using DSM‐5 criteria was high (89.7%), and exposure to multiple traumatic event types was the norm. PTSD caseness was determined using Same Event (i.e., all symptom criteria met to the same event type) and Composite Event (i.e., symptom criteria met to a combination of event types) definitions. Lifetime, past‐12‐month, and past 6‐month PTSD prevalence using the Same Event definition for DSM‐5 was 8.3%, 4.7%, and 3.8% respectively. All 6 DSM‐5 prevalence estimates were slightly lower than their DSM‐IV counterparts, although only 2 of these differences were statistically significant. DSM‐5 PTSD prevalence was higher among women than among men, and prevalence increased with greater traumatic event exposure. Major reasons individuals met DSM‐IV criteria, but not DSM‐5 criteria were the exclusion of nonaccidental, nonviolent deaths from Criterion A, and the new requirement of at least 1 active avoidance symptom.     

Development of a single numerical expression for the results of multiple screening tests for immune complexes in diabetic patients: use in statistical comparison of clinically and biochemically defined patient populations

A series of 88 diabetic patients were studied for the presence of soluble immune complexes, proteinuria, microangiopathy, and diabetic complications. Results of the five different assays for immune complexes were analyzed individually, and four combinations of the individual results (i.e. four different immune complex "scores") were also analyzed. The only assay which consistently discriminated between the different patient groups was the PEG-IgG test, in which a ratio between the amount of IgG precipitated with 3% PEG 6000 and the serum concentration of IgG is determined. In contrast, all four of the immune complex "scores" detected significant differences between patients with and without the clinical or biochemical parameter in question. One combination, designated as the "weighted and corrected IC score", gave a particularly high probability of detecting differences between groups. These results indicate that proper compilation of the results of a battery of immune complex screening assays can provide definite advantages over the results of individual tests for the investigation of correlations between the presence of soluble immune complexes and the course and pathology of various diseases.     

Does Physical Activity in Adolescence Have Site‐Specific and Sex‐Specific Benefits on Young Adult Bone Size,Content, and Estimated Strength?

The long‐term benefits of habitual physical activity during adolescence on adult bone structure and strength are poorly understood. We investigated whether physically active adolescents had greater bone size, density, content, and estimated bone strength in young adulthood when compared to their peers who were inactive during adolescence. Peripheral quantitative computed tomography (pQCT) was used to measure the tibia and radius of 122 (73 females) participants (age mean ± SD, 29.3 ± 2.3 years) of the Saskatchewan Pediatric Bone Mineral Accrual Study (PBMAS). Total bone area (ToA), cortical density (CoD), cortical area (CoA), cortical content (CoC), and estimated bone strength in torsion (SSI_p) and muscle area (MuA) were measured at the diaphyses (66% tibia and 65% radius). Total density (ToD), trabecular density (TrD), trabecular content (TrC), and estimated bone strength in compression (BSI_c) were measured at the distal ends (4%). Participants were grouped by their adolescent physical activity (PA) levels (inactive, average, and active) based on mean PA Z‐scores obtained from serial questionnaire assessments completed during adolescence. We compared adult bone outcomes across adolescent PA groups in each sex using analysis of covariance followed by post hoc pairwise comparisons with Bonferroni adjustments. When adjusted for adult height, MuA, and PA, adult males who were more physically active than their peers in adolescence had 13% greater adjusted torsional bone strength (SSI_p, p < 0.05) and 10% greater adjusted ToA (p < 0.05) at the tibia diaphysis. Females who were more active in adolescence had 10% larger adjusted CoA (p < 0.05), 12% greater adjusted CoC (p < 0.05) at the tibia diaphysis, and 3% greater adjusted TrC (p < 0.05) at the distal tibia when compared to their inactive peers. Benefits to tibia bone size, content, and strength in those who were more active during adolescence seemed to persist into young adulthood, with greater ToA and SSI_p in males, and greater CoA, CoC, and TrC in females. © 2014 American Society for Bone and Mineral Research.