Purging of acute myeloid leukemic cells by ether lipids and hyperthermia

Ether lipids (EL) and hyperthermia have been shown to possess a relatively selective cytotoxicity to leukemic cells. In this study, the combined effects of EL (ET-18-OCH3, ET-16-NHCOCH3, or BM 41.440) and hyperthermia on the growth of hematopoietic progenitors, myeloid leukemic cell lines, and leukemic cells obtained from patients with acute myeloid leukemia (AML) were examined to determine if this combination resulted in a greater selective killing of leukemic cells than that achieved by either EL or heat alone. When the cells were treated simultaneously with EL (50 micrograms/mL) and hyperthermia (42 degrees C) for one hour, the killing of leukemic cell line cells was enhanced considerably. Among the three EL, however, the combination of ET-18-OCH3 and heat seemed to be the most cytotoxic to leukemic cell line cells with no effect on the growth of hematopoietic progenitors. An increase in the duration of treatment with ET-18-OCH3 to four hours with heat added during the last hour resulted in a further reduction of leukemic cell line cells while sparing 50% of hematopoietic progenitors after cryopreservation. The combined treatment with ET-18-OCH3 and heat also inhibited the growth of leukemic progenitors obtained from AML patients by 97% to 100%. These data indicate that the combined treatment with EL and hyperthermia might offer an efficient means to eliminate myeloid leukemic cells in vitro.     

Significance of left atrial volume in patients < 20 years of age with hypertrophic cardiomyopathy

Left atrial (LA) enlargement is an indicator of chronic elevation in left ventricular (LV) end-diastolic pressure as well as diastolic dysfunction. There is a lack of data on the significance of LA volume in the pediatric population. The objective of this study was to elucidate the relation between LA volume and diastolic dysfunction, clinical symptoms, and exercise capacity in young patients with hypertrophic cardiomyopathy. All patients aged <20 years with obstructive hypertrophic cardiomyopathy who underwent evaluation at the Mayo Clinic from 2002 to 2006 were retrospectively identified. Reviews of the LA volume index and other traditional diastolic Doppler echocardiographic parameters, as well as clinical data, were performed. A total of 88 patients (66 male) were studied. The median age at evaluation was 14 years. The mean LA volume index was 39 +/- 19 ml/m(2). Additional echocardiographic parameters included a mean LV outflow gradient of 55 +/- 51 mm Hg, a mean E/E' ratio of 14.0 +/- 7.6, and a mean maximal septal wall thickness of 23 +/- 9 mm. On univariate linear regression analysis, LA volume index had an excellent correlation with diastolic dysfunction grade (p <0.001, r(2) = 0.6), LV outflow tract gradient, mitral E/E', and the degree of mitral regurgitation. LA volume index was also positively associated with symptom score (p = 0.005) and maximal oxygen consumption on exercise test (n = 22; p = 0.01). On multivariate analysis, LA volume index was related to diastolic dysfunction grade (p <0.001) and mean mitral regurgitation grade (p = 0.05). In conclusion, this study demonstrates the potential clinical importance of LA volume index in pediatric hypertrophic cardiomyopathy as a marker of the severity of underlying diastolic dysfunction, symptom score, and decreased exercise capacity. LA volume index has significant diagnostic and prognostic value in these patients.     

Feather mercury concentrations in North American raptors sampled at migration monitoring stations

We assessed total mercury (THg) concentrations in breast feathers of diurnal North American raptors collected at migration monitoring stations. For 9 species in the Pacific Flyway, we found species and age influenced feather THg concentrations whereas sex did not. Feather THg concentrations µg/g dry weight (dw) averaged (least squares mean ± standard error) higher for raptors that generally consume > 75% avian prey (sharp-shinned hawk Accipiter striatus: n = 113; 4.35 ± 0.45 µg/g dw, peregrine falcon Falco peregrinus: n = 12; 3.93 ± 1.11 µg/g dw, Cooper’s hawk Accipiter cooperii: n = 20; 2.35 ± 0.50 µg/g dw, and merlin Falco columbarius: n = 59; 1.75 ± 0.28 µg/g dw) than for raptors that generally consume < 75% avian prey (northern harrier Circus hudsonius: n = 112; 0.75 ± 0.10 µg/g dw, red-tailed hawk Buteo jamaicensis: n = 109; 0.56 ± 0.06 µg/g dw, American kestrel Falco sparverius: n = 16; 0.57 ± 0.14 µg/g dw, prairie falcon Falco mexicanus: n = 10; 0.41 ± 0.13 µg/g dw) except for red-shouldered hawks Buteo lineatus: n = 10; 1.94 ± 0.61 µg/g dw. Feather THg concentrations spanning 13-years (2002–2014) in the Pacific Flyway differed among 3 species, where THg increased for juvenile northern harrier, decreased for adult red-tailed hawk, and showed no trend for adult sharp-shinned hawk. Mean feather THg concentrations in juvenile merlin were greater in the Mississippi Flyway (n = 56; 2.14 ± 0.18 µg/g dw) than those in the Pacific Flyway (n = 49; 1.15 ± 0.11 µg/g dw) and Intermountain Flyway (n = 23; 1.14 ± 0.16 µg/g dw), and Atlantic Flyway (n = 38; 1.75 ± 0.19 µg/g dw) averaged greater than the Pacific Flyway. Our results indicate that raptor migration monitoring stations provide a cost-effective sampling opportunity for biomonitoring environmental contaminants within and between distinct migration corridors and across time.

     

Sclerostin and Pref-1 have differential effects on bone mineral density and strength parameters in adolescent athletes compared with non-athletes

Summary

Excessive exercise can have detrimental effects on bone; however, the mechanisms leading to bone loss are not well understood. Sclerostin and preadipocyte factor (Pref)-1 are two hormones which inhibit bone formation. The present study demonstrates that these hormones may have differential effects in athletes as compared to non-athletes.

Introduction

Exercise activity is common in female adolescents, however, excessive exercise can have detrimental effects on bone mineral density (BMD). Mechanisms underlying this decrease in bone mass are not well understood. We investigated the effects of sclerostin, a potent inhibitor of bone formation via WNT signaling inhibition, and Pref-1, a suppressor of osteoblast differentiation, on BMD, bone turnover markers and bone strength in adolescent athletes.

Methods

We studied 50 adolescents between 15–21 years of age: 17 amenorrheic athletes (AA), 17 eumenorrheic athletes (EA), and 16 nonathletic controls (NA). We measured spine and hip BMD by dual energy x-ray absorptiometry and estimated failure load and stiffness at the distal radius and tibia using micro-finite element analysis. We also measured fasting sclerostin, Pref-1, N-terminal propeptide of type 1 procollagen, and C-terminal collagen cross-links levels.

Results

Sclerostin levels were higher in AA and EA compared with NA (AA: 0.42?±?0.15 ng/mL, EA: 0.44?±?0.09 ng/mL, NA: 0.33?±?0.14 ng/mL; p?=?0.047). In EA, sclerostin was positively associated with lumbar spine (LS) BMD and its Z-score (R?=?0.52, p?=?0.03 and R?=?0.55, p?=?0.02, respectively) whereas in NA, sclerostin was inversely associated with LS BMD (R?=??0.61, p?=?0.01). Pref-1 levels were similar in all three groups and there were significant inverse associations between Pref-1, BMD, and estimated bone strength in NA.

Conclusions

Sclerostin and Pref-1 may have differential effects on bone in adolescent athletes compared to non-athletes.