Visceral Adipose Tissue Quantification Using Lunar Prodigy

A dual-energy X-ray absorptiometry (DXA) application to measure visceral adipose tissue (VAT) in the android region of a total body DXA scan has recently been developed. This new application, CoreScan, has been validated on the Lunar iDXA (GE Healthcare, Madison, WI) densitometer against volumetric computed tomography. The geometric assumptions underlying the CoreScan model are the same on the Prodigy (GE Healthcare, Madison, WI) densitometer. However, differences between the peak X-ray voltage and detector array configurations may lead to differences in VAT quantification. The purpose of this study was to evaluate the agreement of Prodigy and iDXA CoreScan values and to characterize differences in VAT precision between the instruments. Data from volunteers with paired Prodigy and iDXA measurements were used to define empirical adjustments to the VAT algorithm parameters (n = 59) and validate performance on Prodigy (n = 62). Prodigy VAT measurements were highly correlated to iDXA (r = 0.984). The mean of the Prodigy-iDXA VAT volume differences was ?13.8 cm³ with a 95% confidence interval of ?45 to +17 cm³. The Bland-Altman 95% limits of agreement for the 2 methods were ?252 to +224 cm³. Measurement of short-term precision showed that measurement error variance on iDXA was smaller (p < 0.01) than Prodigy (coefficient of variance: 7.3% vs 9.8%). Precision results are in agreement with previous reports on the differences between Prodigy and iDXA for body composition measures. Prodigy and iDXA measures of VAT are similar, but the lower precision of the Prodigy may require investigators to target larger changes in VAT.     

Association between initial morphine intake and body weight change,acoustic startle reflex and drug seeking in rats

Rationale

Although chronic use of opiates can induce physical dependence and addiction, individual differences contributing to these symptoms are largely unknown.

Objectives

Using intravenous morphine self-administration (MSA), we investigated whether individual differences in drug intake are associated with weight change, acoustic startle reflex (ASR), pre-pulse inhibition (PPI), and drug seeking during spontaneous withdrawal.

Methods

Male Sprague-Dawley rats self-administered morphine (0.5 mg/kg/infusion) or saline for 3 weeks (4–6 h/day, 5 days/week) and drug intake and body weight were monitored daily. The ASR and the PPI (baseline, 1 day and 1 week) and drug seeking (1 week) were measured during spontaneous withdrawal.

Results

Morphine animals did not gain weight (101 %?±?0.69), while the control animals did (115 %?±?1.06) after 3 weeks of self-administration. The ASR and the PPI were not significantly different between morphine and saline animals in 1-day or 1-week withdrawal. However, individual differences in initial (first 10 min), but not total (4–6 h), morphine intake of the daily sessions were positively correlated with weight change (r?=?0.437, p?=?0.037) and drug seeking (r?=?0.424, p?=?0.035) while inversely correlated with the ASR (r?=??0.544, p?=?0.005) in 1-week withdrawal from chronic morphine.

Conclusions

A subgroup of animals that self-administered a larger amount of morphine at the beginning of the daily sessions exhibited subsequent weight gain, reduced ASR, and enhanced drug seeking in morphine withdrawal. Thus, individual differences in initial morphine intake may reveal a novel behavioral phenotype in opioid addiction.     

Dynamics of telomere shortening in neutrophils and T lymphocytes during ageing and the relationship to skewed X chromosome inactivation patterns

Human haemopoiesis undergoes profound changes throughout life, resulting in compromised regenerative capacity of haemopoietic stem cells. It has been suggested that telomere shortening results in senescence of haemopoietic stem cell subsets and may influence the balance between stem cell renewal and proliferation. Telomere length and telomerase activity was measured in whole blood leucocytes, neutrophils and T cells from cord blood and individuals aged from 1 year to 96 years. Rapid telomere shortening [700 base pairs (bp)] was demonstrated in the first year of life, followed by a gradual decline of 31 bp/year. T cells were shown to have longer telomeres than neutrophils (mean difference 372 bp, P = < 0.001) but demonstrated similar rates of shortening (20 +/- 0.3 bp/year vs. 22 +/- 0.3 bp/year). Telomerase was detectable in T cells but not in neutrophils, suggesting that telomerase is not the rate-limiting step for regulation of telomere length in haemopoietic cells. Stem cell utilization as measured by X chromosome inactivation patterns was found to be independent of telomere length. This supports the concept that age-dependent skewed haemopoiesis is the result of random stem cell loss or X-allelic exclusion rather than telomeric senescence. These studies provide insight into the ageing process and a reference point for evaluating replicative stress in individuals of different age groups.     

Evaluation of drugs for elimination of leukemic cells from the bone marrow of patients with acute leukemia

Relatively nonmyelotoxic drugs and drug combinations were investigated for their ability to eliminate malignant cells from human bone marrow. In vitro 90% inhibitory concentration (IC90) doses were established on granulocyte macrophage colony-forming units (GM-CFU) in culture of bone marrow by using the GM-CFU assay for the following drugs: 4- hydroperoxycyclophosphamide (4-HC), Adriamycin, L-asparaginase, bleomycin, hydrocortisone, VP-16, spirogermanium, Taxol, and vincristine. The leukemic cell kill efficiency of these drugs at IC90 doses was compared with that of 4-HC on acute lymphoid leukemia (ALL) cell lines by using the limiting-dilution assay. Under these conditions, no single drug was superior to 4-HC. To increase the in vitro effect in leukemic cell kill, combinations of vincristine with hydrocortisone, Adriamycin, VP-16, and 4-HC were investigated. Vincristine at 1 to 5 micrograms/mL increased the marrow cytotoxicity of hydrocortisone, Adriamycin, and VP-16, but it was protective (subadditive) with 4-HC. Vincristine and 4-HC in combination was additive to supraadditive on ALL cell lines, increased the leukemic cell kill by one to two logs above 4-HC alone at IC90 doses (P less than .05), and was not affected by the addition of excess marrow cells. The recommended doses for chemopurging in clinical studies are vincristine, 1 to 5 micrograms/mL, plus 4-HC, 5 micrograms/mL.