Hydroxyurea in the management of the hematologic complications of chronic granulocytic leukemia

The effect of hydroxyurea in 35 patients with chronic granulocytic leukemia (CGL), who either had entered an accelerated phase of the disease or had experienced excessive myelosuppression following alkylating agents, was studied. By either intravenous or oral administration, the drug was successful in reducing peripheral leukocyte and blast counts in all cases and in reducing splenomegaly in 13 of 17 patients. The median duration of disease control was 75 days in myeloproliferative acceleration and 27 days in frank blastic transformation. Mild nausea and vomiting were experienced by most patients, but reversible bone marrow suppression occured in only three patients. The drug proved useful in 19 patients who demonstrated myeloproliferative acceleration, especially in controlling excessive leukocytosis and/or thrombocytosis. Rapid reduction of an elevated blast cell count was achieved in nine patients who presented in blastic crisis, in an attempt to eliminate the associated risk of cerebral vascular leukostasis. Five patients who required treatment for their disease following splenectomy in the chronic phase were also well controlled. Hydroxyurea appears to have a definite role in the management of these hematologic complications of CGL.     

Biocompatibility evaluation of a new bioresorbable pin for membrane fixation

The aim of this study was to morphometrically analyze the tissue response to a customized pin obtained from devitalized bovine cortical bone (DBCB-pin) implanted in the subcutaneous tissue of rats, as well as to assess its microstructural aspect by scanning electron microscopy (SEM). The pins were implanted in the subcutaneous tissue of 20 rats, which were killed at 7, 14, 28 and 60 days (5 rats/period) after implantation. In the subcutaneous tissue, DBCB-pin promoted the formation of a fibrous capsule. At 7 days, capsule showed thickness of 70 ± 3.2 μm with higher density of newly formed capillaries and smaller density of collagen fibers. Between 14 and 60 days, more organized fibrous capsule exhibited smaller thickness (53 ± 5.5 μm) with higher density of fibroblasts and collagen fibers. In this period, a small and slow bioresorption of the DBCB-pin by macrophages and rare multinucleated giant cells without tissue damage was observed. The thickness of DBCB-pin resorbed was in mean only of 9.3 μm. During all experimental periods not occurred presence of immune reaction cells as lymphocytes and plasma cells. It was concluded that the pin derived from cortical bovine bone was well tolerated by subcutaneous tissue of rats and slowly resorbed could be an alternative material for membrane fixation in the guided tissue regeneration procedures.     

Down-regulation of expression of osteoblast and osteocyte markers in periodontal tissues associated with the spontaneous alveolar bone loss of interleukin-10 knockout mice

Claudino M, Garlet TP, Cardoso CRB, de Assis GF, Taga R, Cunha FQ, Silva JS, Garlet GP. Down-regulation of expression of osteoblast and osteocyte markers in periodontal tissues associated with the spontaneous alveolar bone loss of interleukin-10 knockout mice. Eur J Oral Sci 2010; 118: 19–28. © 2010 The Authors. Journal compilation © 2010 Eur J Oral Sci
The aim of this study was to unravel the mechanisms by which interleukin (IL)-10, a potent pleiotropic cytokine, modulates alveolar bone homeostasis in C57BL/6 wild-type (WT) and IL-10 knockout (IL-10 KO) mice, evaluated at 8, 24, and 48 wk of age. Interleukin-10 KO mice presented significant alveolar bone loss when compared with WT mice, and this was not associated with changes in leukocyte counts or bacterial load. The levels of expression of messenger RNA (mRNA) for tumor necrosis factor-α (TNF-α), IL-1β, IL-6, transforming growth factor-β (TGF-β), receptor activator of nuclear factor κB ligand (RANKL), osteoprotegerin (OPG), and matrix metalloproteinase 13 (MMP13) were similar between both strains, whereas a significant decrease of tissue inhibitor of metalloproteinase 1 (TIMP1) mRNA expression was found at 48 wk in IL-10 KO mice. The osteoblast markers core binding factor alpha1 (CBFA1) and type I collagen (COL-I) were expressed at similar levels in both strains, whereas the levels of alkaline phosphatase (ALP) and osteocalcin (OCN), and those of the osteocyte markers phosphate-regulating gene endopeptidases (PHEX) and dentin matrix protein 1 (DMP1) were significantly lower in IL-10 KO mice. Our results demonstrate that the alveolar bone loss in the absence of IL-10 was associated with a reduced expression of osteoblast and osteocyte markers, an effect independent of microbial, inflammatory or bone-resorptive pathways.     

Evaluation of the chronic toxicity and oncogenicity of N,N-diethyl-m- toluamide (DEET)

Chronic toxicity and/or oncogenicity studies were conducted in rats, mice, and dogs with the insect repellent DEET. DEET was mixed in the diet and administered to CD rats for two years at concentrations that corresponded to dosage levels of 10, 30 or 100 mg/kg/day for males and 30, 100, or 400 mg/kg/day for females; to CD-1 mice for 18 months at dosage levels of 250, 500, or 1000 mg/kg/day; and to dogs for one year, via gelatin capsules, at dosage levels of 30, 100, or 400 mg/kg/day. In the rodent studies, each group consisted of 60 animals of each sex, and two concurrent independent control groups, each containing 60 animals/sex were included in each study. Each group in the dog study consisted of four male and four female dogs and one control group was included in the study. Treatment-related effects were observed at the highest dose level in all three studies. For rats, the effects included decreases in body weight and food consumption and an increase in serum cholesterol in females only. In mice, the effects observed were decreases in body weight and food consumption in both sexes. The effects observed in dogs included increased incidences of emesis and ptyalism, and levels of transient reduction in hemoglobin and hematocrit, increased alkaline phosphatase (males only), decreased cholesterol, and increased potassium. One male dog in the high-dose group also exhibited ataxia, tremors, abnormal head movements, and/or convulsions on several occasions during the study. The highest no- observed-effect levels (NO-ELs) for rats, mice and dogs were determined to be 100, 500, and 100 mg/kg/day, respectively. No specific target organ toxicity or oncogenicity was observed in any of the studies.      

Initiation of health-behaviour change among employees participating in a web-based health risk assessment with tailored feedback

Background  

Primary prevention programs at the worksite can improve employee health and reduce the burden of cardiovascular disease. Programs that include a web-based health risk assessment (HRA) with tailored feedback hold the advantage of simultaneously increasing awareness of risk and enhancing initiation of health-behaviour change. In this study we evaluated initial health-behaviour change among employees who voluntarily participated in such a HRA program.