Thrombopoietin stimulates megakaryocytopoiesis, myelopoiesis, and expansion of CD34+ progenitor cells from single CD34+Thy-1+Lin- primitive progenitor cells

Thrombopoietin (TPO) or MpI ligand is known to stimulate megakaryocyte (MK) proliferation and differentiation. To identify the earliest human hematopoietic cells on which TPO acts, we cultured single CD34+Thy- 1+Lin- adult bone marrow cells in the presence of TPO alone, with TPO and interleukin-3 (IL-3), or with TPO and c-kit ligand (KL) in the presence of a murine stromal cell line (Sys1). Two distinct growth morphologies were observed: expansion of up to 200 blast cells with subsequent differentiation to large refractile CD41b+ MKs within 3 weeks or expansion to 200-10,000 blast cells, up to 25% of which expressed CD34. The latter blast cell expansions occurred over a 3- to 6-week period without obvious MK differentiation. Morphological staining, analysis of surface marker expression, and colony formation analysis revealed that these populations consisted predominantly of cells committed to the myelomonocytic lineage. The addition of IL-3 to TPO-containing cultures increased the extent of proliferation of single cells, whereas addition of KL increased the percentage of CD34+ cells among the expanding cell populations. Production of multiple colony- forming unit-MK from single CD34+Thy-1+Lin- cells in the presence of TPO was also demonstrated. In limiting dilution assays of CD34+Lin- cells, TPO was found to increase the size and frequency of cobblestone areas at 4 weeks in stromal cultures in the presence of leukemia inhibitory factor and IL-6. In stroma-free cultures, TPO activated a quiescent CD34+Lin-Rhodamine 123lo subset of primitive hematopoietic progenitor cells into cycle, without loss of CD34 expression. These data demonstrate that TPO acts directly on and supports division of cells more primitive than those committed to the MK lineage.     

Selecting Constant Work Rates for Endurance Testing in COPD: The Role of the Power-Duration Relationship

Constant work rate (CWR) exercise testing is highly responsive to therapeutic interventions and reveals physiological and functional benefits. No consensus exists, however, regarding optimal methods for selecting the pre-intervention work rate. We postulate that a CWR whose tolerated duration (t_lim) is 6 minutes (WR₆) may provide a useful interventional study baseline. WR₆ can be extracted from the power-duration relationship, but requires 4 CWR tests. We sought to develop prediction algorithms for easier WR₆ identification using backward stepwise linear regression, one in 69 COPD patients (FEV₁ 45 ± 15% pred) and another in 30 healthy subjects (HLTH), in whom cycle ergometer ramp incremental (RI) and CWR tests with t_lim of ～6 minutes had been performed. Demographics, pulmonary function, and RI responses were used as predictors. We validated these algorithms against power-duration measurements in 27 COPD and 30 HLTH (critical power 43 ± 18W and 231 ± 43W; curvature constant 5.1 ± 2.7 kJ and 18.5 ± 3.1 kJ, respectively). This analysis revealed that, on average, only corrected peak work rate ( = WR_peak–1 min × WR_slope) in RI was required to predict WR₆ (COPD SEE = 5.0W; HLTH SEE = 5.6W; R² > 0.96; p < 0.001). In the validation set, predicted and actual WR₆ were strongly correlated (COPD R² = 0.937; HLTH 0.978; p < 0.001). However, in COPD, unlike in HLTH, there was a wide range of t_lim values at predicted WR₆: COPD 8.3 ± 4.1 min (range 3.6 to 22.2 min), and HLTH 5.5 ± 0.7 min (range 3.9 to 7.0 min). This analysis indicates that corrected WR_peak in an incremental test can yield an acceptable basis for calculating endurance testing work rate in HLTH, but not in COPD patients.     

Assessment of family history of colorectal cancer in primary care: Perceptions of first degree relatives of people with colorectal cancer

Objective

First degree relatives (FDRs) of someone with colorectal cancer (CRC) are at increased risk of the disease. In this study we examine the factors associated with discussing family history of CRC with a health professional.

Methods

People with CRC, recruited through the population-based Victorian Cancer Registry in Australia, were asked to refer FDRs to the study. Eight hundred and nineteen FDRs completed a telephone interview.

Results

Thirty-six percent of FDRs recalled ever being asked about their family history of bowel cancer by a health professional. Factors associated with having this discussion were being aged 50–60 years, having a university education, being in the potentially high risk category, being very worried about getting bowel cancer and knowing that family history increases risk through discussions with family, friends or their own education.

Conclusion

Despite evidence that doctor endorsement is a key factor in the uptake of CRC screening, our study shows that the majority of FDRs do not recall being asked by a health professional about their family history.

Practice implications

There is a need to identify the most appropriate method to improve rates of health professional discussion of family history with relatives of CRC patients in order to improve screening rates.     

Wound healing effect of methanolic leaf extract of Napoleona vogelii(Family:Lecythidaceae) in rats

Objective:To investigate the wound healing properly of Napoleona vogelii leaf extract in folkloric medicine.Methods:Roth sexes of adult albino rats(n=25) were used in this study and another group(n=30) were subjected to acute toxicity test(LD_(50)) of the plant extract.For the LD_(50),three randomized groups of 5 rats were first treated with 10,100,1 000 mg/kg body weight(bw),orally.This w as followed by a second treatment of 1500,3000,and 5 000 mg/kg bw of the leaf extract with continual monitoring of the animals for mortality or non-mortality.Incision wounds(1.3cm) were created on the skin of five groups of 5 rals using surgical blade under anesthesia.The first group was topically treated with petroleum jelly alone,group 2 was topically applied 400 mg/mL w/v of the reference drug,Neobaein,while group 3-5 were topically treated with 5-50 mg/mL w/v of the plant extract,respectively.Results:The percentage yield of the extract was 49.80%w/w dry matter.The phytochemical analysis revealed several bioactive constituents including glycosides,tannins,alkaloids,perpenoids.saponins,steroids,proteins,and carbohydrates.The LD_(50) was beyond our experimental limit and was not determined.Increased concentrations(5,20,and 50mg/mL w/v) of the extract had significant(ANOVA,P0.05) healing effect on the incision wounds giving rise to 125%-140% while treatmentawith Neobacin resulted in 150% healing effect on the third treatment regimen compared to the control(100%).Conclusions:These data indicate that Napoleona vogelii leaf extract contains potent bioactive compounds containing wound healing activity,substantiating its use as a wound healer in folkloric medicine.