Hydroxyurea-Increased Fetal Hemoglobin Is Associated with Less Organ Damage and Longer Survival in Adults with Sickle Cell Anemia

Background

Adults with sickle cell anemia (HbSS) are inconsistently treated with hydroxyurea.

Objectives

We retrospectively evaluated the effects of elevating fetal hemoglobin with hydroxyurea on organ damage and survival in patients enrolled in our screening study between 2001 and 2010.

Methods

An electronic medical record facilitated development of a database for comparison of study parameters based on hydroxyurea exposure and dose. This study is registered with ClinicalTrials.gov, number NCT00011648.

Results

Three hundred eighty-three adults with homozygous sickle cell disease were analyzed with 59 deaths during study follow-up. Cox regression analysis revealed deceased subjects had more hepatic dysfunction (elevated alkaline phosphatase, Hazard Ratio = 1.005, 95% CI 1.003–1.006, p<0.0.0001), kidney dysfunction (elevated creatinine, Hazard Ratio = 1.13, 95% CI 1.00–1.27, p = 0.043), and cardiopulmonary dysfunction (elevated tricuspid jet velocity on echocardiogram, Hazard Ratio = 2.22, 1.23–4.02, p = 0.0082). Sixty-six percent of subjects were treated with hydroxyurea, although only 66% of those received a dose within the recommended therapeutic range. Hydroxyurea use was associated with improved survival (Hazard Ratio = 0.58, 95% CI 0.34–0.97, p = 0.040). This effect was most pronounced in those taking the recommended dose of 15–35 mg/kg/day (Hazard Ratio 0.36, 95% CI 0.17–0.73, p = 0.0050). Hydroxyurea use was not associated with changes in organ function over time. Further, subjects with higher fetal hemoglobin responses to hydroxyurea were more likely to survive (p = 0.0004). While alkaline phosphatase was lowest in patients with the best fetal hemoglobin response (95.4 versus 123.6, p = 0.0065 and 96.1 versus 113.6U/L, p = 0.041 at first and last visits, respectively), other markers of organ damage were not consistently improved over time in patients with the highest fetal hemoglobin levels.

Conclusions

Our data suggest that adults should be treated with the maximum tolerated hydroxyurea dose, ideally before organ damage occurs. Prospective studies are indicated to validate these findings.     

Haptoglobin and CCR2 receptor expression in ovarian cancer cells that were exposed to ascitic fluid: Exploring a new role of haptoglobin in the tumoral microenvironment

Haptoglobin (Hp) is an acute-phase protein that is produced by the liver to capture the iron that is present in the blood circulation, thus avoiding its accumulation in the blood. Moreover, Hp has been detected in a wide variety of tissues, in which it performs various functions. In addition, this protein is considered a potential biomarker in many diseases, such as cancer, including ovarian carcinoma; however, its participation in the cancerous processes has not yet been determined. The objective of this work was to demonstrate the expression of Hp and its receptor CCR2 in the ovarian cancer cells and its possible involvement in the process of cell migration through changes in the rearrangement of the actin cytoskeleton using western blot and wound-healing assays and confirming by confocal microscopy. Ovarian cancer cells express both Hp and its receptor CCR2 but only after exposure to ascitic fluid, inducing moderated cell migration. However, when the cells are exposed to exogenous Hp, the expression of CCR2 is induced together with drastic changes in the actin cytoskeleton rearrangement. At the same time, Hp induced cell migration in a much more efficient manner than did ascitic fluid. These effects were blocked when the CCR2 synthetic antagonist RS102895 was used to pretreat the cells. These results suggest that Hp-induced changes in the cell morphology, actin cytoskeleton structure, and migration ability of tumor cells, is possibly “preparing” these cells for the potential induction of the metastatic phenotype.     

Cage enrichment with paper tissue, but not plastic tunnels, increases variability in mouse model of asthma

Environmental enrichment, besides having a great impact on animal welfare, can also be a potential variable in experimental research. Thus, we investigated whether enrichment of cages with paper tissues or plastic tunnels affects scientific outcome in the well-described mouse model of allergic asthma. BALB/cJ mice were introduced to paper tissues as nesting material, transparent plastic tunnels serving as shelters or kept in non-enriched cages. Afterwards, mice were sensitized to chicken egg ovalbumin (OVA) precipitated in aluminium sulphate and then intranasally challenged with OVA to induce allergic lung inflammation. Mice housed in cages enriched with paper tissues, but not with plastic tunnels, had increased total cell number, eosinophil number and IL-13 concentration in bronchoalveolar lavage fluid in comparison with the non-enriched control group. These results indicate that the effect of environmental enrichment on mice asthma models depends on the type of enrichment used. Therefore, it is important to consider the potential effects of any environmental enrichment on animal welfare and more importantly, on research results in order to standardize and obtain more accurate data from rodent studies.     

First Philippine record of the parasitoid,Comperiella sp. (Hymenoptera: Encyrtidae): a potential biocontrol agent against Aspidiotus rigidus (Hemiptera: Diaspididae)

The encyrtid genus Comperiella Howard has so far not been reported in the Philippines, where there is currently an outbreak of the coconut scale insect Aspidiotus rigidus Reyne particularly in the southern parts of the island of Luzon and in some areas in Mindanao. Among Comperiella species, only C. unifasciata Ishii has been reported as a parasitoid of A. rigidus. We report not only new sightings of this parasitoid genus in the Philippines from surveys conducted in parts of the provinces of Laguna and Batangas, but also the discovery of a possibly new species that, like C. unifasciata, has been found to parasitize A. rigidus at a high rate. These findings have presented a potential of biological control against the coconut scale insect problem that has threatened the coconut industry in the country.     

Enhanced secretory ability for the human factor VIII light chain produced in baculovirus-infected insect cells

The light and truncated heavy chains of human factor VIII, expressed separately in baculovirus-infected insect cells, exhibited different secretory behaviour when compared with each other and with a biologically active fusion molecule of the truncated heavy and light chains.The light chain was very efficiently secreted into culture medium, as judged by high extracellular protein levels and the absence of evidence for light chain retention within cells.Alternatively, proteins containing the heavy chain sequence were poorly secreted and appeared to be sequestered within cells, suggesting that regions within the heavy chain are responsible for the low levels of secreted protein which have generally been observed for recombinant factor VIII.     

重庆市蕨类植物区系调查和分析

重庆市有野生蕨类植物47科120属604种(含变种及以下分类单位)。其科属优势明显,其中蹄盖蕨科、金星蕨科、鳞毛蕨科和水龙骨科4个科包含了49属337种,占重庆市蕨类植物属、种总数的40.83%和55.79%;特有现象明显,地方特有种十分丰富,中国特有种和地方特有种类分别达到164种和33种;蕨类植物区系具有古老、孑遗和原始性等特点,表现出一定的热带性质或热带亲缘。